Inhibition of N-, P/Q- and other types of Ca2+ channels in rat hippocampal nerve terminals by the adenosine A1 receptor (original) (raw)
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Neuroscience Letters, 1996
We determined that activation of adenosine A1 receptors in striatal synaptosomes with 100 nM N6-cyclopentyladenosine (CPA) inhibited both the release of endogenous glutamate and the increase of intracellular free Ca 2÷ concentration ([Ca2÷]i), due to 4aminopyridine (4-AP) stimulation, by 28 and 19%, respectively. Furthermore, CPA enhanced the inhibition of endogenous glutamate release due to o:-conotoxin GVIA (oJ-Cgtx GVIA), oJ-Cgtx MVIIC or ~-Cgtx GVIA plus ~-Cgtx MVIIC. Similar effects were observed in the [Ca2+]i signal. The inhibitory effects of CPA and o~-Cgtx GVIA were additive, but the effects of CPA and ~-Cgtx MVIIC were only partially additive. These results suggest that P/Q-type Ca 2÷ channels and other type(s) of Ca 2÷ channel(s), coupled to glutamate release, are inhibited subsequently to activation of adenosine A1 receptors.
The Journal of Physiology, 2000
Magnocellular neurones in the hypothalamic supraoptic nucleus (SON) synthesize arginine vasopressin and oxytocin. These peptides are released into the systemic circulation from axon terminals located in the neurohypophysis, and the released amount is closely related to the electrical activity of SON neurones (Bourque, 1991; Leng & Brown, 1997). This electrical activity is regulated by humoral factors and synaptic neurotransmitters/ neuromodulators, such as glutamate and ã_aminobutyric acid, various peptides and other physiological active substances including purinergic agents (Hatton, 1990; Brann, 1995; Shibuya et al. 1999). In various regions of the mammalian central nervous system (CNS), adenosine is well known to act as a neuro-transmitterÏneuromodulator (Fredholm & Dunwiddie, 1988). Adenosine modulates neural excitability and acts as a neural sleep factor in basal forebrain and mesopontine cholinergic neurones (Rainnie et al. 1994), as an endogenous anticonvulsant in the hippocampus and amygdala (Dragunow, 1988), as a modulator of LTP in the hippocampus (de Mendon ca & Ribeiro, 1994) and as a neuroprotective agent in the hippocampus (Dragunow & Faull, 1988). At present, classification of adenosine receptors is based on both their protein sequences and their affinity for a variety of ligands (Fredholm et al. 1994). Four subtypes of adenosine receptor have been cloned and pharmacologically characterized: A1, A2a, A2b and A× receptors. A1 and A× receptors are thought to be coupled to Gé andÏor Gï proteins, while A2a and A2b are coupled to Gs protein (Fredholm et al. 1994; Palmer & Stiles, 1995). The various effects of adenosine on neuronal activity are thought to occur through the modulation of Ca¥ channels andÏor K¤ channels (Fredholm & Dunwiddie, 1988; Fredholm et al. 1994; Palmer & Stiles, 1995). It has been reported that adenosine modulates voltage-dependent calcium channels (VDCCs) in the postsynaptic membrane of many different
Drug Development Research, 1993
Adenosine acts in at least three different ways at A, receptors in order to reduce excitability and signal transfer. In the hippocampus, it causes i) a steady state outward (potassium) current which is blocked by barium ions and not sensitive to voltage; ii) an increase in the calciumand cyclic AMP-dependent current IAHP which is responsible for a long lasting afterhyperpolarization and the accommodation of action potential firing; iii) a presynaptic reduction of excitatory but not inhibitory transmitter release. The mechanism of this effect is unclear. It is, in contrast to the former, not sensitive to pertussis toxin. When the adenosine elicited potassium currents at the postsynaptic site are blocked, slow inward currents, normally carried by calcium, are unaffected by adenosine. A2 receptor mediated actions have not been found in the hippocampus. While the precise analysis of these effects has been done largely on rats they were all found in human hippocampal slices as well. o 1993 Wiley-Liss, Inc.
Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices
The Journal of physiology, 1985
Intracellular recordings with a bridge amplifier of CA1 pyramidal neurones in vitro were employed to study the mechanisms of action of exogenously applied adenosine in the hippocampal slice preparation of the rat. Adenosine enhanced the calcium-dependent, long-duration after-hyperpolarization (a.h.p.) at least in part by a reduction in the rate of decay of the a.h.p. Both the reduced rate of decay and that of the control can be described with a single exponential. Antagonism of the calcium-dependent potassium current (and as a result, the a.h.p.) by bath application of CdCl2 or intracellular injection of EGTA (ethyleneglycolbis-(beta-aminoethyl ether)N,N'-tetraacetic acid) did not reduce the adenosine-evoked hyperpolarization or decrease in input resistance. Similarly, TEA (tetraethylammonium), which antagonizes both the voltage- and calcium-sensitive, delayed, outward rectification, had no effect on the adenosine-evoked changes in resting membrane properties. Adenosine did not ...
The Journal of Physiology, 2002
Effects of adenosine on voltage-gated Ca 2+ channel currents and on arginine vasopressin (AVP) and oxytocin (OT) release from isolated neurohypophysial (NH) terminals of the rat were investigated using perforated-patch clamp recordings and hormone-specific radioimmunoassays. Adenosine, but not adenosine 5‚-triphosphate (ATP), dose-dependently and reversibly inhibited the transient component of the whole-terminal Ba 2+ currents, with an IC 50 of 0.875 mM. Adenosine strongly inhibited, in a dose-dependent manner (IC 50 = 2.67 mM), depolarization-triggered AVP and OT release from isolated NH terminals. Adenosine and the N-type Ca 2+ channel blocker v-conotoxin GVIA, but not other Ca 2+ channel-type antagonists, inhibited the same transient component of the Ba 2+ current. Other components such as the L-, Q-and R-type channels, however, were insensitive to adenosine. Similarly, only adenosine and v-conotoxin GVIA were able to inhibit the same component of AVP release. A 1 receptor agonists, but not other purinoceptor-type agonists, inhibited the same transient component of the Ba 2+ current as adenosine. Furthermore, the A 1 receptor antagonist 8-cyclopentyltheophylline (CPT), but not the A 2 receptor antagonist 3, 7-dimethyl-1-propargylxanthine (DMPGX), reversed inhibition of this current component by adenosine. The inhibition of AVP and OT release also appeared to be via the A 1 receptor, since it was reversed by CPT. We therefore conclude that adenosine, acting via A 1 receptors, specifically blocks the terminal N-type Ca 2+ channel thus leading to inhibition of the release of both AVP and OT.
Neuroscience, 2002
AbstractöAdenosine tonically inhibits synaptic transmission through actions at A 1 receptors. It also facilitates synaptic transmission, but it is unclear if this facilitation results from pre-and/or postsynaptic A 2A receptor activation or from indirect control of inhibitory GABAergic transmission. The A 2A receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission in the CA1 area of rat hippocampal slices (by 14%), independent of whether or not GABAergic transmission was blocked by the GABA A and GABA B receptor antagonists, picrotoxin (50 WM) and CGP 55845 (1 WM), respectively. CGS 21680 (10 nM) also inhibited paired-pulse facilitation by 12%, an e¡ect prevented by the A 2A receptor antagonist, ZM 241385 (20 nM). These e¡ects of CGS 21680 (10 nM) were occluded by adenosine deaminase (2 U/ml) and were made to reappear upon direct activation of A 1 receptors with N 6 -cyclopentyladenosine (CPA, 6 nM). CGS 21680 (10 nM) only facilitated (by 17%) the K þ -evoked release of glutamate from superfused hippocampal synaptosomes in the presence of 100 nM CPA. This e¡ect of CGS 21680 (10 nM), in contrast to the isoproterenol (30 WM) facilitation of glutamate release, was prevented by the protein kinase C inhibitors, chelerythrine (6 WM) and bisindolylmaleimide (1 WM), but not by the protein kinase A inhibitor, H-89 (1 WM). Isoproterenol (30 WM), but not CGS 21680 (10^300 nM), enhanced synaptosomal cAMP levels, indicating that the CGS 21680-induced facilitation of glutamate release involves a cAMP-independent protein kinase C activation. To discard any direct e¡ect of CGS 21680 on adenosine A 1 receptor, we also show that in autoradiography experiments CGS 21680 only displaced the adenosine A 1 receptor antagonist, 1,3dipropyl-8-cyclopentyladenosine ([ 3 H]DPCPX, 0.5 nM) with an EC 50 of 1 WM in all brain areas studied and CGS 21680 (30 nM) failed to change the ability of CPA to displace DPCPX (1 nM) binding to CHO cells stably transfected with A 1 receptors.
Developmental Brain Research, 1998
. We compared the effects of the adenosine A1 receptor activation on the postsynaptic potentials psps recorded from the CA3 area of Ž . immature postnatal days 10-20 and adult rat hippocampal neurons in vitro. The adenosine A1 receptor agonist 2-phenyl-isopropyl-Ž . adenosine PIA, 1 mM depressed the stimulus-induced psps less in immature and more in adult neurons. In the presence of the GABA A Ž . receptor antagonist bicuculline methiodide BMI, 10 mM , PIA reduced the duration and number of action potentials of the Ž . stimulus-induced paroxysmal depolarizations PDs in immature neurons, while it blocked PDs in adult neurons. Spontaneous Ž . Ž . BMI-induced PDs, were blocked by PIA in less than half 5r12 immature and all 6r6 adult neurons. The adenosine A1 receptor Ž . antagonist 8-cyclopentyl-1,3-dipropylxanthine DPCPX, 1 mM enhanced the stimulus-induced psps in immature and adult neurons alike;
British Journal of Pharmacology, 2000
We investigated how manipulations of the degree of activation of adenosine A 1 and A 2A receptors in¯uences the action of the neuropeptide, calcitonin gene-related peptide (CGRP) on synaptic transmission in hippocampal slices. Field excitatory post-synaptic potentials (EPSPs) from the CA1 area were recorded. 2 When applied alone, CGRP (1 ± 30 nM) was without eect on ®eld EPSPs. However, CGRP (10 ± 30 nM) signi®cantly increased the ®eld EPSP slope when applied to hippocampal slices in the presence of the A 1 receptor antagonist, 1,3-dipropyl-8-cyclopenthyl xanthine (DPCPX, 10 nM), or in the presence of the A 2A adenosine receptor agonist CGS 21680 (10 nM). 3 The A 2A receptor antagonist, ZM 241385 (10 nM) as well as adenosine deaminase (ADA, 2 U ml 71), prevented the enhancement of ®eld EPSP slope caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this eect of CGRP requires the concomitant activation of A 2A adenosine receptors by endogenous adenosine. 4 The protein kinase-A inhibitors, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 10 mM) and adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS, 50 mM), as well as the inhibitor of ATP-sensitive potassium (K ATP) channels, glibenclamide (30 mM), prevented the facilitation of synaptic transmission caused by CGRP (30 nM) in the presence of DPCPX (10 nM), suggesting that this eect of CGRP involves both K ATP channels and protein kinase-A. 5 It is concluded that the ability of CGRP to facilitate synaptic transmission in the CA1 area of the hippocampus is under tight control by adenosine, with tonic A 1 receptor activation by endogenous adenosine`braking' the action of CGRP, and the A 2A receptors triggering this action.
Adenosine A2 receptors modulate hippocampal synaptic transmission via a cyclic-AMP-dependent pathway
Neuroscience, 1998
Blockade of adenosine A 2 receptors has been shown to significantly reduce the level of tetanus-induced long-term potentiation in area CA1 of rat hippocampus [Kessey K. et al. (1997) Brain Res. 756, 184-190;) Biochem. biophys. Res. Commun. 181, 1010-1014. In the present study, the effects of A 2 receptor activation and blockade on the modulation of normal synaptic transmission and tetanus-induced long-term potentiation were examined at the Schaffer-CA1 synapse in rat hippocampal slices. A 2 receptor activation reversibly enhanced synaptic transmission evoked by low-frequency test pulses as measured by the dendritic field excitatory postsynaptic potential. In the presence of A 1 receptor blockade, A 2 activation further enhanced the excitatory postsynaptic potential, while A 2 receptor blockade resulted in a reversible decrease of the excitatory postsynaptic potential. The A 2a receptor agonist, CGS21680, had no effect on the excitatory postsynaptic potential, suggesting that tonic activation of A 2b receptors contributes to synaptic transmission under normal physiological conditions. Furthermore, we investigated the contribution of A 2 receptors to the level of tetanus-induced long-term potentiation. Under control conditions, a single tetanus potentiated the excitatory postsynaptic potential by 63.5% relative to baseline 30 min post-tetanus. In contrast, tetanus-induced long-term potentiation during A 2 blockade was 21.3%. A 2 receptor activation increased the level of tetanus-induced long-term potentiation to 90.2%. Because A 2 receptors are known to stimulate cyclic-AMP accumulation, the possible involvement of cyclic-AMP was examined. Forskolin, a direct adenylate cyclase activator, and 8-bromo-cyclic-AMP, a membrane-permeable analog of cyclic-AMP, were able to reconstitute tetanusinduced long-term potentiation during A 2 receptor blockade; however, the inactive analog 1,9-dideoxyforskolin had no effect, indicating that the effects of A 2 activation on synaptic transmission were mediated largely through the regulation of intracellular cyclic-AMP.