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Multiple opiate binding sites in the central nervous system of the rabbit. Large predominance of a mu subtype in the cerebellum and characterization of a kappa subtype in the thalamus.
Mol Pharmacol. 1983 Jul; 24(1):23-9.MP

Abstract

We have compared the binding characteristics of [3H]etorphine, a nonselective mu-, delta-, and kappa-opiate agonist, with those of [3H]Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH ([3H]DAGO), a selective mu-agonist, in rabbit cerebellar and thalamic membranes. We have also examined the ability of various unlabeled opioid ligands to compete with the binding of [3H]etorphine in the two preparations. In cerebellar membranes, [3H]DAGO(Kd = 0.7 nM) labels slightly fewer sites than does [3H]etorphine (Kd = 0.06 nM): 0.18 versus 0.24 pmole/mg of protein. In addition, competition studies indicate that up to 75% of the [3H]etorphine binding sites in this preparation display (a) high apparent affinity for unlabeled DAGO and (b) higher apparent affinity for morphine, the prototypical mu-agonist, than for Tyr-D-Ala-Gly-Phe-D-Leu (DADL), a delta-agonist. Together, these results suggest that the rabbit cerebellum contains a very high proportion (0.7-0.8) of mu-opiate binding sites. In thalamic membranes, [3H]DAGO (Kd = 1.1 nM) labels considerably fewer sites than does [3H]etorphine (Kd = 0.08 nM): 0.09 versus 0.27 pmole/mg of protein. In this preparation, the competition curves of DAGO and of DADL resolve binding of [3H]etorphine into two components. The first component accounts for 40-50% of total binding and reflects the interaction of [3H]etorphine with mu-opiate binding sites. The second component (up to 50% of total binding) is unaffected in the presence of DADL at concentrations (1-10 microM) that rule out binding of [3H]etorphine to mu- and delta-opiate binding sites. It disappears readily in the presence of very low concentrations (Ki less than 1 nM) of benzomorphan opiates (bremazocine, cyclazocine, and ethylketocyclazocine) yet it is relatively insensitive to inhibition by mu- and delta-agonists. This second component may therefore reflect [3H]etorphine's interaction with a kappa-opiate binding site. The kappa-opiate binding site is assayed for as that site which binds [3H]etorphine (0.5 nM) in the presence of either DADL (2 microM) or 10 microM of another enkephalin: Tyr-D-Ser-Gly-Phe-Leu-Thr. We find that, in the rabbit central nervous system, the thalamus, followed by frontal cortex and caudate nucleus, shows the highest content of kappa-opiate binding sites.

Authors

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Pub Type(s)

Journal Article

Language

eng

PubMed ID

6306437

Citation

Meunier, J C., et al. "Multiple Opiate Binding Sites in the Central Nervous System of the Rabbit. Large Predominance of a Mu Subtype in the Cerebellum and Characterization of a Kappa Subtype in the Thalamus." Molecular Pharmacology, vol. 24, no. 1, 1983, pp. 23-9.
Meunier JC, Kouakou Y, Puget A, et al. Multiple opiate binding sites in the central nervous system of the rabbit. Large predominance of a mu subtype in the cerebellum and characterization of a kappa subtype in the thalamus. Mol Pharmacol. 1983;24(1):23-9.
Meunier, J. C., Kouakou, Y., Puget, A., & Moisand, C. (1983). Multiple opiate binding sites in the central nervous system of the rabbit. Large predominance of a mu subtype in the cerebellum and characterization of a kappa subtype in the thalamus. Molecular Pharmacology, 24(1), 23-9.
Meunier JC, et al. Multiple Opiate Binding Sites in the Central Nervous System of the Rabbit. Large Predominance of a Mu Subtype in the Cerebellum and Characterization of a Kappa Subtype in the Thalamus. Mol Pharmacol. 1983;24(1):23-9. PubMed PMID: 6306437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple opiate binding sites in the central nervous system of the rabbit. Large predominance of a mu subtype in the cerebellum and characterization of a kappa subtype in the thalamus. AU - Meunier,J C, AU - Kouakou,Y, AU - Puget,A, AU - Moisand,C, PY - 1983/7/1/pubmed PY - 1983/7/1/medline PY - 1983/7/1/entrez SP - 23 EP - 9 JF - Molecular pharmacology JO - Mol Pharmacol VL - 24 IS - 1 N2 - We have compared the binding characteristics of [3H]etorphine, a nonselective mu-, delta-, and kappa-opiate agonist, with those of [3H]Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH ([3H]DAGO), a selective mu-agonist, in rabbit cerebellar and thalamic membranes. We have also examined the ability of various unlabeled opioid ligands to compete with the binding of [3H]etorphine in the two preparations. In cerebellar membranes, [3H]DAGO(Kd = 0.7 nM) labels slightly fewer sites than does [3H]etorphine (Kd = 0.06 nM): 0.18 versus 0.24 pmole/mg of protein. In addition, competition studies indicate that up to 75% of the [3H]etorphine binding sites in this preparation display (a) high apparent affinity for unlabeled DAGO and (b) higher apparent affinity for morphine, the prototypical mu-agonist, than for Tyr-D-Ala-Gly-Phe-D-Leu (DADL), a delta-agonist. Together, these results suggest that the rabbit cerebellum contains a very high proportion (0.7-0.8) of mu-opiate binding sites. In thalamic membranes, [3H]DAGO (Kd = 1.1 nM) labels considerably fewer sites than does [3H]etorphine (Kd = 0.08 nM): 0.09 versus 0.27 pmole/mg of protein. In this preparation, the competition curves of DAGO and of DADL resolve binding of [3H]etorphine into two components. The first component accounts for 40-50% of total binding and reflects the interaction of [3H]etorphine with mu-opiate binding sites. The second component (up to 50% of total binding) is unaffected in the presence of DADL at concentrations (1-10 microM) that rule out binding of [3H]etorphine to mu- and delta-opiate binding sites. It disappears readily in the presence of very low concentrations (Ki less than 1 nM) of benzomorphan opiates (bremazocine, cyclazocine, and ethylketocyclazocine) yet it is relatively insensitive to inhibition by mu- and delta-agonists. This second component may therefore reflect [3H]etorphine's interaction with a kappa-opiate binding site. The kappa-opiate binding site is assayed for as that site which binds [3H]etorphine (0.5 nM) in the presence of either DADL (2 microM) or 10 microM of another enkephalin: Tyr-D-Ser-Gly-Phe-Leu-Thr. We find that, in the rabbit central nervous system, the thalamus, followed by frontal cortex and caudate nucleus, shows the highest content of kappa-opiate binding sites. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/6306437/Multiple_opiate_binding_sites_in_the_central_nervous_system_of_the_rabbit__Large_predominance_of_a_mu_subtype_in_the_cerebellum_and_characterization_of_a_kappa_subtype_in_the_thalamus_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6306437 DB - PRIME DP - Unbound Medicine ER -