Abstract
When 3H-etorphine was administered to rats in a pharmacologically effective dose (0.75 Μg/kg intracisternally), the labeled drug was concentrated in synaptic membrane fractions isolated from the brains of rats killed 10 min after etorphine injection. Pretreatment of the animals with the narcotic antagonists naloxone, diprenorphine or l-cyclorphan, blocked the pharmacological responses to etorphine and reduced 3H-etorphine binding in the membrane fractions. The differences between 3H-etorphine bound in synaptic membranes of rats treated with d-cyclorphan (inactive isomer) and l-cyclorphan (active antagonist) were in the same range as the reductions in etorphine binding in antagonist-treated rats, indicating that stereospecific and pharmacologically-specific binding sites in synaptic membranes in vivo were of the same magnitude: about 0.04 pmol/g brain.
Similar content being viewed by others
References
Clouet, D. H., Williams, N.: Localization in brain particulate fractions of narcotic analgesic drugs administered intracisternally to rats. Biochem. Pharmacol. 22, 1283–1293 (1973)
DeRobertis, E., Alberici, M., Rodriguez de Lores Arnaiz, G., Azcurra, J. M.: Isolation of different types of synaptic membranes from the brain cortex. Life Sci. 5, 577–582 (1966)
Eddy, N. B., Leimbach, D.: Synthetic analgesics. II. Dithienylbutenyl- and dithenylbutyl-amines. J. Pharmacol. exp. Ther. 107, 385–373 (1953)
Goldstein, A., Lowney, L. I., Pal, B. K.: Stereospecific and non-specific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain. Proc. nat. Acad. Sci. (Wash.) 68, 1742–1747 (1971)
Hertz, A., Teschemacher, H. J.: Activities and sites of antinociceptive action of morphine-like analgesics. In: Advances in drug research, N. J. Harper and A. B. Simonds, eds., pp. 79–119. New York: Academic Press 1971
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)
Mulé, S. J.: Physiological disposition of narcotic agonists and antagonists. In: Narcotic drug: biochemical pharmacology, D. H. Clouet, ed., pp. 99–121. New York: Plenum Press 1971
Mulé, S. J., Casella, G., Clouet, D. H.: Localization of levo 3H-methadone in isolated synaptic membranes of rat brain. In: Proceedings, NAS-NRC Committee on Problems in Drug Dependence, pp. 322–339 (1972)
Mulé, S. J., Casella, G., Clouet, D. H.: Localization of narcotic analgesics in synaptic membranes of rat brain. Res. Commun. Chem. Path. Pharmacol. 9, 55–77 (1974)
Pert, C. B., Snyder, S. H.: Opiate receptor: demonstration in nervous tissue. Science 179, 1011–1014 (1973a)
Pert, C. B., Snyder, S. H.: Properties of Opiate receptor binding in rat brain. Proc. nat. Acad. Sci. (Wash.) 70, 2243–2247 (1973b)
Pert, C. B., Pasternak, G., Snyder, S. H.: Opiate agonists and antagonists discriminated by receptor binding in brain. Science 182, 1359–1361 (1973)
Pert, C. B., Snowman, A. M., Snyder, S. H.: Localization of opiate receptor binding in synaptic membrane fractions of rat brain. Brain Res. 70, 184–188 (1974)
Rodriguez de Lores Arnaiz, G., Alberici, M., DeRobertis, E.: Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex. J. Neurochem. 14, 215–225 (1967)
Simon, E. J., Hiller, J. M., Edelman, I.: Stereospecific binding of the potent narcotic analgesic 3H-etorphine in rat brain homogenates. Proc. nat. Acad. Sci. (Wash.) 70, 1947–1949 (1973)
Simon, E. J., Hiller, J. M., Groth, J., Edelman, I.: Further properties of stereospecific opiate binding sites in rat brain: On the nature of the sodium effect. J. Pharmacol. exp. Ther. 192, 531–537 (1975)
Terenius, L.: Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta pharmacol. (Kbh.) 32, 317–320 (1973)
Wong, D. T., Horng, J. S.: Stereospecific interaction of opiate narcotics in binding of 3H-dihydromorphine to membranes of ratbrain. Life Sci. 13, 1543–1556 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mulé, S.J., Casella, G. & Clouet, D.H. The specificity of binding of the narcotic agonist etorphine in synaptic membranes of rat brain in vivo . Psychopharmacologia 44, 125–129 (1975). https://doi.org/10.1007/BF00420998
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00420998