Differential effects of sodium on two types of opiate binding sites (original) (raw)
Related papers
effect of α-adrenergic blockers on naloxone-binding in braiN
Biochemical Pharmacology, 1974
In several recent studies, we have shown that a-adrenergic blocking agents possess a degree of antinociceptive activity themselves, markedly increase morphine's analgetic and toxic effects, and effectively suppress the expression of the narcotic withdrawal syndrome in the rat (1,2,3). Since B-adrenergic blocking agents and numerous other agents possessed none of these properties, these data suggest that the narcotics and a-adrenergic blockers may be closely related. However, since all of the data up to the present are indirect, we cannot rule out the possibility that the interaction we have observed between these two classes of drugs merely represents the summation of two totally independent processes. The purpose of the studies described in this paper was to obtain more direct evidence of an interaction between morphine and a-adrenergic blocking agents. Pert and Synder (4,5) previously have demonstrated that stereospecific binding of naloxone occurs in rat brain homogenates and that various narcotic agonists and antagonists effectively reduce naloxone-binding. We have employed this preparation to examine whether a-adrenergic blockers would displace naloxone from the so-called "opiate receptor."
Regional saturation studies of [3H]naloxone binding in the naive, dependent and withdrawal states
Brain Research, 1985
We have examined the saturation features (K d and Bronx) of [3H]naloxone binding in rat brain regions in cytoarchitectonically intact tissues of naive, morphine dependent and precipitated withdrawal states using quantitative film autoradiography. Sixty-one saturation experiments in 13 regions of naive rat brains yielded monophasic Eadie-Hofstee plots with a mean (+ S,D.) K a of 1.87 + 0.87 nM and a mean Bma x (+ S.D.) of 101 + 66 fmol/mg. The 61 K d values in naive rats described a normal distribution of regional binding affinities that may reflect the biological variation of a single high affinity binding site. Similar studies in the morphine dependent and prec~p, itated withdrawal states showed no apparent changes in either the K d or Bm~ of regional [aH]naloxone binding. The possibility that in vitro preincubation of tissue sections masked potential alterations in [aH]naloxone binding was examined in competition studies of both morphine and naloxone for 2.0 nM [3H]naloxone binding to striatal sections. Preincubation had no effect on the ability of either opiate agonist or antagonist to compete for [3H]naloxone binding in the naive, morphine dependent or precipitated withdrawal states. The regional data comparing K d and Bma x for [3H]naloxone binding in naive, morphine dependent and precipitated withdrawal states eliminated the possibility that previous efforts to demonstrate alterations in opiate binding were confounded by homogenization and/or limitations of gross dissection. Our data suggest that either potential changes in antagonist binding in dependent and withdrawal states can only be demonstrated under strict in VlVO conditions or that post-binding transduction mechanisms are the sites of adaptive changes in naloxone sensitivity in the states of opiate dependence and withdrawal. * Preliminary reports of these data were given at the 13th Society for Neuroscience Meeting (1983) and the Wenner-Gren Symposium, Stockholm, Sweden (May, 1984).
Opiate receptor: cooperativity of binding observed in brain slices
Proceedings of the National Academy of Sciences of the United States of America, 1977
Kinetic constants for binding of 3H-labeled morphine and naloxone were determined from Hill plot analyses and from experiments in which the concentration of tritiated drug was constant and that of nonlabeled drug varied. With brain slices, the binding of either drug exhibited strong positive cooperativity (Hill slope >3); this was not observed in brain homogenates. Thus, in slices the relationship between opiate binding site and ligand may be more relevant physiologically and pharmacologically.
The distribution of multiple opiate receptors in bovine brain
Brain Research, 1981
The distribution of # and 6 opiate receptors in bovine brain has been investigated using the selective radioligands [3H]morphine and D-[aH]AIa z, D-Leu'~-enkephalin. Their distributions were found to vary independently through different brain areas with up to a 10-fold difference between the ratio of bt to 6 binding sites for the substantia nigra and the dentate gyrus of the hippocampus.
Reassessment of opioid binding sites in the rat brain
Neuropeptides, 1986
Opioid binding sites have been characterized pharmacologically in membranes from different areas of the rat brain. Delta,mu and sites belonging to the kappa family (Kl,K2,K3) have been detected.Delta sites were more abundant in cortex and striatum,mu sites in striatum and hypothalamus,while kappa binding site concentration was higher in deeper enkephalic structures (brainstem,cerebellum,hypothalamus) and the pituitary gland. A distinct distribution of each subtype of the kappa site was found: kappa 1 sites were higher in the spinal cord,kappa 2 sites in the brainstem and kappa 3 sites in cerebellum. The distribution of delta and kappa sites in the central nervous system was correlated with the distribution of proenkephalin-A derived peptides and precursors, suggesting that these peptides could be their endogenous ligands.
Opiate receptor localization in rat cerebral cortex
The Journal of Comparative Neurology, 1983
The differential distributions of ['Hlnaloxone-labeled and [3H]D-Ala-D-Leu-enkephalin-labeled opiate receptors in rat cerebral cortex were localized autoradiographically and quantified by grain counting and computerized densitometry. In addition, receptor distributions were compared to terminal patterns of thalamocortical projections labeled by axoplasmic transport of ['Hlamino acids. Opiate receptors labeled with ['Hlnaloxone in a mu ligand selectivity pattern show striking laminar heterogeneity and are densest in limbic cortical areas, intermediate in the motor cortex, and fewest in the primary sensory areas. By contrast, opiate receptors labeled with ['HID-Ala2-D-Le~~enkephalin in a delta ligand selectivity pattern are much more homogeneously distributed across both regions and laminae within regions.
European Journal of Pharmacology, 1980
Localization of naloxone-sensitive [3H]dihydromorphine binding sites within the hippocampus of the rat, European J. Pharmaeol. 68 (1980) 175--179. In vitro radioautographic experiments were performed on coronal rat brain slices to determine the precise localization of [3H]dihydromorphine binding sites sensitive to naloxone, within the hippocampus. Binding was observed in all cell fields and in dentate gyrus (DG) in the order CA2 > CA1 > CA3 > DG. Within each cell field the density of receptors was greatest in the stratum pyramidale, which in field CA2 was 77% as dense as the striatum. The existence of a dense population of opiate binding sites within the hippocampus is consistent with the view that this structure is involved in opiate actions.