Donna Curtis - Academia.edu (original) (raw)
Papers by Donna Curtis
Brain Research, 1985
Experiments were undertaken to determine the site of action of securinine and related convulsant ... more Experiments were undertaken to determine the site of action of securinine and related convulsant indolizidines. All of these compounds induced tonic seizures in mice, with CD50 values ranging from 11 to 87 mg/kg. The CDs0 for bicuculline was found to be 8 mg/kg. Equilibrium binding assays revealed that securinine and dihydrosecurinine inhibit [3H]GABA binding to rat brain membranes with an IC50 of approximately 50 aM, which is some 7 times less potent than bicuculline. Allosecurinine and virosecurinine have IC50 values greater than 1 mM. Both dihydrosecurinine and securinine inhibited GABA-stimulated benzodiazepine binding in rat brain membranes, though they were somewhat weaker than bicuculline in this respect. Other binding assays revealed that securinine and its analogs were inactive as inhibitors of bicuculline-insensitive GABA binding, benzodiazepine, cholinergic muscarinic, and fl-adrenergic receptor binding. In addition, while thiocyanate ion increased the apparent binding potency of bicucuiline 10-fold, it had little effect on that of securinine. Extracellular electrophysiological studies on neurons in the cat spinal cord indi6ated that securinine and dihydrosecurinine blocked the inhibitory action of GABA while having no effect on that of glycine. Allo-and virosecurinine were much less active as GABA receptor antagonists in this test. These results suggest that, like bicuculline, securinine and dihydrosecurinine are selective antagonists of GABA recognition sites on mammalian central neurons.
Neuroscience Letters, 1988
When administered microelectrophoretically, a sulphonic acid derivative of baclofen, 3-amino-2-(4... more When administered microelectrophoretically, a sulphonic acid derivative of baclofen, 3-amino-2-(4chlorophenyl)-2-hydroxy-propylsulphonic acid, reversibly reduced the presynaptic reduction by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in low threshold primary afferent fibres of the cat as well as the postsynaptic depression by (-)-baciofen of the firing of these neurones. This compound, 2-hydroxy-saclofen, may be useful in assessing the physiological significance of central baclofen receptors.
European Journal of Pharmacology, 1986
In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduc... more In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduced the inhibitory effects on neuronal firing of both glycine and GABA.
Neuroscience Letters, 1986
hk'v wor~Zs." cat spinal cord glycine },-aminobutyric acid (GABA) pyridazinyl derivatives of GABA... more hk'v wor~Zs." cat spinal cord glycine },-aminobutyric acid (GABA) pyridazinyl derivatives of GABA 2-(carboxy-3'-propyl)-3-amino-6-paramethoxy-phenylpyridazinium bromide of tw~ arylaminopyridazine derivatives of 7-aminobutyric acid (GABA) tested as antagonists of the inhibitory actions of glycine and GABA in the spinal cord of pentobarbilone-anaesthetized cats. one SR95531 was sufficiently selective to be of use in microelectrophoretic investigations of GABA-mediated synaplic transmission. 0304-3940/865 03.50
Brain Research, 1987
Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium ... more Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium and calcium, reduced the depolarization by microelectrophoretic y-aminobutyric acid (GABA) and piperidine-4-sulphonic acid of the central terminations of muscle group Ia primary afferent fibres in the cat spinal cord without affecting the inhibition by GABA of the firing of spinal interneurones. There thus appears to be a difference in either the interaction of GABA with recognition sites, or in the mechanism by which such interaction activates chloride ionophores, at GABA-mediated bicuculline-sensitive synapses on the central terminals of peripheral primary afferent neurones and those on neurones located within the central nervous system.
![Research paper thumbnail of Baclofen antagonism by 4-amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid in the cat spinal cord](https://attachments.academia-assets.com/49022750/thumbnails/1.jpg)
](Neuroscience Letters, 1989
Key wor~&: Baclofen: 4-Amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid; Cat spinal cord; Prim... more Key wor~&: Baclofen: 4-Amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid; Cat spinal cord; Primary afferent excitation When administered microelectrophoretically, 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (MBFG) reversibly reduced the presynaptic depression by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in muscle low-threshold afferent fibres of the cat as well as the postsynaptic depression by ( )-baclofen of the firing of these neurones. MBFG, as an antagonist of ( -)-baclofen, may be useful in investigating the structure activity relationships of central and peripheral baclofen receptors.
Experimental Brain Research, 1995
An extracellular microstimulation technique has been used to investigate and compare the properti... more An extracellular microstimulation technique has been used to investigate and compare the properties of group I primary afferent myelinated fibres in the dorsal column and group Ia unmyelinated terminations in the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium. Fibres were distinguished from terminations on the basis of location, anodic blocking factor and sensitivity to GABAA mimetics. The recovery curves of threshold following an orthodromic impulse provided an estimate of both action potential duration and rate of repolarization. The action potentials of group Ia terminations were of briefer duration (by a factor of approximately 2) with more rapid rates of repolarization (factor of approximately 3) than those of the myelinated fibres. The prolongation of termination but not fibre action potentials by microelectrophoretic tetraethylammonium and 4-aminopyridine indicated the presence of voltage-activated potassium channels in the termination membrane. Differences in the effects on Ia termination action potentials of depolarizations (reductions in threshold) associated with a preceding action potential, synaptically released GABA, microelectrophoretic piperidine-4-sulphonic acid or dl-homocysteic acid suggest that an increase in termination membrane conductance is the major factor in the reduction of transmitter release during the activation of presynaptic GABAA receptors.
Experimental Brain Research, 1989
In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of... more In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of the terminations of extensor muscle group Ia afferent fibres, produced by tetanic stimulation of either the appropriate peripheral nerve or the central termination, were associated with parallel changes in the bicuculline-sensitive reduction in electrical threshold of the termination produced synaptically by impulses in flexor muscle low threshold afferent fibres (primary afferent depolarization, PAD) or by microelectrophoretic piperidine-4-sulphonic acid (P4S), an analogue of GABA. Since this post-tetanic hyperpolarization (PTH) could be produced by tetanic stimulation of a single termination centrally, and not by peripheral stimulation of heteronymous nerves, it presumably resulted from changes intrinsic to the tetanized termination. Increases in PAD and the effectiveness of P4S were probably associated with post-tetanic activation of an electrogenic Na+/K+ pump as the predominant cause of PTH, whereas decreases may have been largely the consequence of post-tetanic increases in intracellular Ca2+ levels. These results provide further evidence that GABA is the depolarizing transmitter at axo-axonic synapses upon primary afferent terminals, and that the underlying membrane conductance increase has a reversal potential at a more depolarized level than the resting potential.
Proceedings of The Royal Society of London. Series B, Biological Sciences (1934-1990), 1984
Although GABA and piperidine-4-sulphonic acid depolarize I a afferent terminations in the cat spi... more Although GABA and piperidine-4-sulphonic acid depolarize I a afferent terminations in the cat spinal cord by activation of bicuculline-sensitive GABA receptors, no evidence was obtained for a bicuculline-sensitive alteration by either gabamimetic of the electrical threshold of rubrospinal terminations in the spinal intermediate nucleus. The terminal axonal arborizations in the spinal cord of neurons in the red nucleus thus do not have GABA receptors similar to those on the cell bodies. The results are discussed in relation to the depolarizing action of GABA on some central neurons, and on neurons with peripheral cell bodies, and to probable differences in the intracellular chloride content of neurons having peripheral or central cell bodies, and thus of different embryological origin. A presynaptic depolarizing inhibitory process mediated by GABA appears to be confined to the terminals of primary afferent fibres in the mammalian central nervous system.
Experimental Brain Research, 1997
In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, ... more In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.
Experimental Brain Research, 1985
Intravenous baclofen (1–6.25 mg kg-1) substantially reduced the monosynaptic excitation of neuron... more Intravenous baclofen (1–6.25 mg kg-1) substantially reduced the monosynaptic excitation of neurones in the intermediate nucleus of the cat spinal cord by impulses in group I extensor muscle primary afferent fibres, but had little or no effect on excitation by stimulating fibres of the ipsilateral dorsolateral funiculus or the contralateral red nucleus. Relatively low concentrations of baclofen thus appear not to influence the release of excitatory transmitter from the terminals of rubrospinal, corticospinal and long descending propriospinal fibres, in contrast to the reduction of the release of primary afferent transmitters.
Experimental Brain Research, 1986
When administered microelectrophoretically, GABA and the GABA-mimetic piperidine-4-sulphonic acid... more When administered microelectrophoretically, GABA and the GABA-mimetic piperidine-4-sulphonic acid (P4S) appear to have no direct hyperpolarizing or depolarizing effect on the terminations of motor axon collaterals excited electrically in the ventral horn of the lumbar spinal cord of the cat. This lack of effect on axon terminals of motoneurones, which contrasts with the bicuculline-sensitive depolarization by P4S of the spinal terminals of primary afferent fibres, is consistent with previous reports of the probable absence of pharmacologically detectable GABA receptors on the spinal terminals of other central excitatory neurones, namely those of the red and lateral vestibular nuclei.
Brain Research, 1984
Although GABA and piperidine-4-sulphonate depolarize la afferent terminations in the lumbar spina... more Although GABA and piperidine-4-sulphonate depolarize la afferent terminations in the lumbar spinal cord i~y activation ol bicuculline-sensitive GABA receptors, no evidence was obtained for a bicuculline-sensitive alteration by either GABAmimetic of the excitability of vestibulospinal terminations. This suggests that the terminal arborizations of vestibulospinal fibers, unlike their celt bodies, are devoid of GABA receptors having properties similar to those on either central neuron cell bodies, primary afferent cell bodies or their central terminations.
Experimental Brain Research, 1986
When administered microelectrophoretically GABA and piperidine-4-sulphonic acid depolarized the c... more When administered microelectrophoretically GABA and piperidine-4-sulphonic acid depolarized the central terminations of muscle group Ia and Ib afferent fibres in the lumbar intermediate nucleus and Clarke's column of cats anaesthetised with pentobarbitone sodium. Both this depolarization, and primary afferent depolarization, generated by impulses in other primary afferent fibres which produce prolonged bicuculline-sensitive inhibition of the firing of group I afferent fibre-excited interneurones in the intermediate nucleus and cells in Clarke's column, are reduced by microelectrophoretic bicuculline methochloride. Systemically administered (±)-baclofen hydrochloride (maximum dose 8 mg kg−1) depressed the monosynaptic excitation of Clarke's column neurones by impulses in muscle and cutaneous afferent fibres. Microelectrophoretically administered (−)-baclofen reduced the bicuculline-sensitive primary afferent depolarization of group I terminations without, however, reducing the depolarizing action of GABA or piperidine-4-sulphonic acid. The depression by (−)-baclofen of the group I monosynaptic excitation of intermediate nucleus neurones is not reduced by concentrations of bicuculline methochloride adequate to suppress prolonged inhibition of these neurones
Preparative Biochemistry & Biotechnology, 1983
A general method is described which allows the identification and preparation of peptides contain... more A general method is described which allows the identification and preparation of peptides containing any amino acid of interest. The method has been applied to isolation of the methionyl peptides from a peptic digest of oxidized bovine rhodopsin. The peptide digestion mixture is first partially separated by ion exchange column chromatography. Location of peptides containing the desired amino acid is performed by amino acid analysis of acid hydrolyzed column fractions by high voltage paper electrophoresis. Peptides are further purified and prepared by peptide mapping, elution, and amino acid analysis using inexpensive high capacity techniques. Peptide sequencing is performed by a manual dansyl-Edman method well adapted for rapidly processing large numbers of samples. The methods are particularly well suited for detection and preparation of peptides containing amino acids for which there is no specific detection method.
Neurochemistry International, 1980
The amino-terminal 39 amino acids of bovine rhodopsin have the sequence
Vision Research, 1982
The covalent sequence of the carboxyl-terminal one-third of bovine rhodopsin has been determined.
European Biophysics Journal With Biophysics Letters, 1983
We have isolated 16 peptides from a cyanogen bromide digest of rhodopsin. These cyanogen bromide ... more We have isolated 16 peptides from a cyanogen bromide digest of rhodopsin. These cyanogen bromide peptides account for the complete composition of the protein. Methionine-containing peptides from other chemical and enzymatic digests of rhodopsin have allowed us to place the cyanogen bromide peptides in order, yielding the sequence of the protein. We have completed the sequence of most of the cyanogen bromide peptides. This information, in conjunction with that from other laboratories, forms the basis for our prediction of the secondary structure of the protein and how it may be arranged in the disk membrane.
Brain Research, 1985
Experiments were undertaken to determine the site of action of securinine and related convulsant ... more Experiments were undertaken to determine the site of action of securinine and related convulsant indolizidines. All of these compounds induced tonic seizures in mice, with CD50 values ranging from 11 to 87 mg/kg. The CDs0 for bicuculline was found to be 8 mg/kg. Equilibrium binding assays revealed that securinine and dihydrosecurinine inhibit [3H]GABA binding to rat brain membranes with an IC50 of approximately 50 aM, which is some 7 times less potent than bicuculline. Allosecurinine and virosecurinine have IC50 values greater than 1 mM. Both dihydrosecurinine and securinine inhibited GABA-stimulated benzodiazepine binding in rat brain membranes, though they were somewhat weaker than bicuculline in this respect. Other binding assays revealed that securinine and its analogs were inactive as inhibitors of bicuculline-insensitive GABA binding, benzodiazepine, cholinergic muscarinic, and fl-adrenergic receptor binding. In addition, while thiocyanate ion increased the apparent binding potency of bicucuiline 10-fold, it had little effect on that of securinine. Extracellular electrophysiological studies on neurons in the cat spinal cord indi6ated that securinine and dihydrosecurinine blocked the inhibitory action of GABA while having no effect on that of glycine. Allo-and virosecurinine were much less active as GABA receptor antagonists in this test. These results suggest that, like bicuculline, securinine and dihydrosecurinine are selective antagonists of GABA recognition sites on mammalian central neurons.
Neuroscience Letters, 1988
When administered microelectrophoretically, a sulphonic acid derivative of baclofen, 3-amino-2-(4... more When administered microelectrophoretically, a sulphonic acid derivative of baclofen, 3-amino-2-(4chlorophenyl)-2-hydroxy-propylsulphonic acid, reversibly reduced the presynaptic reduction by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in low threshold primary afferent fibres of the cat as well as the postsynaptic depression by (-)-baciofen of the firing of these neurones. This compound, 2-hydroxy-saclofen, may be useful in assessing the physiological significance of central baclofen receptors.
European Journal of Pharmacology, 1986
In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduc... more In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduced the inhibitory effects on neuronal firing of both glycine and GABA.
Neuroscience Letters, 1986
hk'v wor~Zs." cat spinal cord glycine },-aminobutyric acid (GABA) pyridazinyl derivatives of GABA... more hk'v wor~Zs." cat spinal cord glycine },-aminobutyric acid (GABA) pyridazinyl derivatives of GABA 2-(carboxy-3'-propyl)-3-amino-6-paramethoxy-phenylpyridazinium bromide of tw~ arylaminopyridazine derivatives of 7-aminobutyric acid (GABA) tested as antagonists of the inhibitory actions of glycine and GABA in the spinal cord of pentobarbilone-anaesthetized cats. one SR95531 was sufficiently selective to be of use in microelectrophoretic investigations of GABA-mediated synaplic transmission. 0304-3940/865 03.50
Brain Research, 1987
Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium ... more Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium and calcium, reduced the depolarization by microelectrophoretic y-aminobutyric acid (GABA) and piperidine-4-sulphonic acid of the central terminations of muscle group Ia primary afferent fibres in the cat spinal cord without affecting the inhibition by GABA of the firing of spinal interneurones. There thus appears to be a difference in either the interaction of GABA with recognition sites, or in the mechanism by which such interaction activates chloride ionophores, at GABA-mediated bicuculline-sensitive synapses on the central terminals of peripheral primary afferent neurones and those on neurones located within the central nervous system.
Neuroscience Letters, 1989
Key wor~&: Baclofen: 4-Amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid; Cat spinal cord; Prim... more Key wor~&: Baclofen: 4-Amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid; Cat spinal cord; Primary afferent excitation When administered microelectrophoretically, 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (MBFG) reversibly reduced the presynaptic depression by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in muscle low-threshold afferent fibres of the cat as well as the postsynaptic depression by ( )-baclofen of the firing of these neurones. MBFG, as an antagonist of ( -)-baclofen, may be useful in investigating the structure activity relationships of central and peripheral baclofen receptors.
Experimental Brain Research, 1995
An extracellular microstimulation technique has been used to investigate and compare the properti... more An extracellular microstimulation technique has been used to investigate and compare the properties of group I primary afferent myelinated fibres in the dorsal column and group Ia unmyelinated terminations in the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium. Fibres were distinguished from terminations on the basis of location, anodic blocking factor and sensitivity to GABAA mimetics. The recovery curves of threshold following an orthodromic impulse provided an estimate of both action potential duration and rate of repolarization. The action potentials of group Ia terminations were of briefer duration (by a factor of approximately 2) with more rapid rates of repolarization (factor of approximately 3) than those of the myelinated fibres. The prolongation of termination but not fibre action potentials by microelectrophoretic tetraethylammonium and 4-aminopyridine indicated the presence of voltage-activated potassium channels in the termination membrane. Differences in the effects on Ia termination action potentials of depolarizations (reductions in threshold) associated with a preceding action potential, synaptically released GABA, microelectrophoretic piperidine-4-sulphonic acid or dl-homocysteic acid suggest that an increase in termination membrane conductance is the major factor in the reduction of transmitter release during the activation of presynaptic GABAA receptors.
Experimental Brain Research, 1989
In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of... more In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of the terminations of extensor muscle group Ia afferent fibres, produced by tetanic stimulation of either the appropriate peripheral nerve or the central termination, were associated with parallel changes in the bicuculline-sensitive reduction in electrical threshold of the termination produced synaptically by impulses in flexor muscle low threshold afferent fibres (primary afferent depolarization, PAD) or by microelectrophoretic piperidine-4-sulphonic acid (P4S), an analogue of GABA. Since this post-tetanic hyperpolarization (PTH) could be produced by tetanic stimulation of a single termination centrally, and not by peripheral stimulation of heteronymous nerves, it presumably resulted from changes intrinsic to the tetanized termination. Increases in PAD and the effectiveness of P4S were probably associated with post-tetanic activation of an electrogenic Na+/K+ pump as the predominant cause of PTH, whereas decreases may have been largely the consequence of post-tetanic increases in intracellular Ca2+ levels. These results provide further evidence that GABA is the depolarizing transmitter at axo-axonic synapses upon primary afferent terminals, and that the underlying membrane conductance increase has a reversal potential at a more depolarized level than the resting potential.
Proceedings of The Royal Society of London. Series B, Biological Sciences (1934-1990), 1984
Although GABA and piperidine-4-sulphonic acid depolarize I a afferent terminations in the cat spi... more Although GABA and piperidine-4-sulphonic acid depolarize I a afferent terminations in the cat spinal cord by activation of bicuculline-sensitive GABA receptors, no evidence was obtained for a bicuculline-sensitive alteration by either gabamimetic of the electrical threshold of rubrospinal terminations in the spinal intermediate nucleus. The terminal axonal arborizations in the spinal cord of neurons in the red nucleus thus do not have GABA receptors similar to those on the cell bodies. The results are discussed in relation to the depolarizing action of GABA on some central neurons, and on neurons with peripheral cell bodies, and to probable differences in the intracellular chloride content of neurons having peripheral or central cell bodies, and thus of different embryological origin. A presynaptic depolarizing inhibitory process mediated by GABA appears to be confined to the terminals of primary afferent fibres in the mammalian central nervous system.
Experimental Brain Research, 1997
In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, ... more In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses.
Experimental Brain Research, 1985
Intravenous baclofen (1–6.25 mg kg-1) substantially reduced the monosynaptic excitation of neuron... more Intravenous baclofen (1–6.25 mg kg-1) substantially reduced the monosynaptic excitation of neurones in the intermediate nucleus of the cat spinal cord by impulses in group I extensor muscle primary afferent fibres, but had little or no effect on excitation by stimulating fibres of the ipsilateral dorsolateral funiculus or the contralateral red nucleus. Relatively low concentrations of baclofen thus appear not to influence the release of excitatory transmitter from the terminals of rubrospinal, corticospinal and long descending propriospinal fibres, in contrast to the reduction of the release of primary afferent transmitters.
Experimental Brain Research, 1986
When administered microelectrophoretically, GABA and the GABA-mimetic piperidine-4-sulphonic acid... more When administered microelectrophoretically, GABA and the GABA-mimetic piperidine-4-sulphonic acid (P4S) appear to have no direct hyperpolarizing or depolarizing effect on the terminations of motor axon collaterals excited electrically in the ventral horn of the lumbar spinal cord of the cat. This lack of effect on axon terminals of motoneurones, which contrasts with the bicuculline-sensitive depolarization by P4S of the spinal terminals of primary afferent fibres, is consistent with previous reports of the probable absence of pharmacologically detectable GABA receptors on the spinal terminals of other central excitatory neurones, namely those of the red and lateral vestibular nuclei.
Brain Research, 1984
Although GABA and piperidine-4-sulphonate depolarize la afferent terminations in the lumbar spina... more Although GABA and piperidine-4-sulphonate depolarize la afferent terminations in the lumbar spinal cord i~y activation ol bicuculline-sensitive GABA receptors, no evidence was obtained for a bicuculline-sensitive alteration by either GABAmimetic of the excitability of vestibulospinal terminations. This suggests that the terminal arborizations of vestibulospinal fibers, unlike their celt bodies, are devoid of GABA receptors having properties similar to those on either central neuron cell bodies, primary afferent cell bodies or their central terminations.
Experimental Brain Research, 1986
When administered microelectrophoretically GABA and piperidine-4-sulphonic acid depolarized the c... more When administered microelectrophoretically GABA and piperidine-4-sulphonic acid depolarized the central terminations of muscle group Ia and Ib afferent fibres in the lumbar intermediate nucleus and Clarke's column of cats anaesthetised with pentobarbitone sodium. Both this depolarization, and primary afferent depolarization, generated by impulses in other primary afferent fibres which produce prolonged bicuculline-sensitive inhibition of the firing of group I afferent fibre-excited interneurones in the intermediate nucleus and cells in Clarke's column, are reduced by microelectrophoretic bicuculline methochloride. Systemically administered (±)-baclofen hydrochloride (maximum dose 8 mg kg−1) depressed the monosynaptic excitation of Clarke's column neurones by impulses in muscle and cutaneous afferent fibres. Microelectrophoretically administered (−)-baclofen reduced the bicuculline-sensitive primary afferent depolarization of group I terminations without, however, reducing the depolarizing action of GABA or piperidine-4-sulphonic acid. The depression by (−)-baclofen of the group I monosynaptic excitation of intermediate nucleus neurones is not reduced by concentrations of bicuculline methochloride adequate to suppress prolonged inhibition of these neurones
Preparative Biochemistry & Biotechnology, 1983
A general method is described which allows the identification and preparation of peptides contain... more A general method is described which allows the identification and preparation of peptides containing any amino acid of interest. The method has been applied to isolation of the methionyl peptides from a peptic digest of oxidized bovine rhodopsin. The peptide digestion mixture is first partially separated by ion exchange column chromatography. Location of peptides containing the desired amino acid is performed by amino acid analysis of acid hydrolyzed column fractions by high voltage paper electrophoresis. Peptides are further purified and prepared by peptide mapping, elution, and amino acid analysis using inexpensive high capacity techniques. Peptide sequencing is performed by a manual dansyl-Edman method well adapted for rapidly processing large numbers of samples. The methods are particularly well suited for detection and preparation of peptides containing amino acids for which there is no specific detection method.
Neurochemistry International, 1980
The amino-terminal 39 amino acids of bovine rhodopsin have the sequence
Vision Research, 1982
The covalent sequence of the carboxyl-terminal one-third of bovine rhodopsin has been determined.
European Biophysics Journal With Biophysics Letters, 1983
We have isolated 16 peptides from a cyanogen bromide digest of rhodopsin. These cyanogen bromide ... more We have isolated 16 peptides from a cyanogen bromide digest of rhodopsin. These cyanogen bromide peptides account for the complete composition of the protein. Methionine-containing peptides from other chemical and enzymatic digests of rhodopsin have allowed us to place the cyanogen bromide peptides in order, yielding the sequence of the protein. We have completed the sequence of most of the cyanogen bromide peptides. This information, in conjunction with that from other laboratories, forms the basis for our prediction of the secondary structure of the protein and how it may be arranged in the disk membrane.