Correlation of dopamine and opiate binding with adenylate cyclase in rat striatum

  • Susan Gentleman

Abstract

The neuroleptic properties of opiate drugs in striatum are well-recognized, but the mechanisms underlying these properties are not known (Lal, 1975). Recently it was reported that opiates inhibit the dopamine (DA)-activated adenylate cyclase of monkey amygdala (Walczak et al., 1979) and rat striatal membranes (Neff et al., 1981). However, no interaction between DA and opiate binding has been observed under standard binding assay conditions (Burt et al., 1976; Snyder et al., 1975). In this study, micromolar, rather than nanomolar, DA binding was measured under assay conditions in which DA activates adenylate cyclase and opiates inhibit the activation. There is a strong correlation between the ability of opiates to block micromolar DA binding and to block activated adenylate cyclase. GTP and dithiothreitol (DTT) appear to be required for these effects. Thus, at least some of the neuroleptic effects of opiates can be attributed to blockade of the D1 receptor as defined by Kebabian and Calne (1979) in striatum.

Keywords

Sucrose Dopamine MgCl2 Tria Monoamine 

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References

  1. Bers, G. and Blecher, M. (1977). Characterization of dopamine binding sites in standard preparations of brain synaptic membranes. Biochem. Pharmacol., 26, 2011–2016.CrossRefPubMedGoogle Scholar
  2. Bradford, M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248–245.CrossRefPubMedGoogle Scholar
  3. Burt, D.R., Creese, I. and Snyder, S.H. (1976) Properties of [3H]haloperidol and [3H]dopamine binding associated with dopamine receptors in calf brain membranes. Mol. Pharmacol., 12, 800–812.PubMedGoogle Scholar
  4. Cooper, D.M.F, Schlegel, W., Lin, M.C. and Rodbell, M. (1979). The fat cell adenylate cyclase system: characterization and manipulation of its bimodal regulation by GTP. J. Biol. Chem., 254, 8927–8931.PubMedGoogle Scholar
  5. Gentleman, S., Parenti, M., Commissiong, J.W. and Neff, N.H. (1981). Dopamine-activated adenylate cyclase of spinal cord: supersensitivity following transection of the cord. Brain Res., in press.Google Scholar
  6. Kebabian, J.W. and Calne, D.B. (1979). Multiple receptors for dopamine. Nature, 277, 93–96.CrossRefPubMedGoogle Scholar
  7. Lal, H. (1975). Minireview: Narcotic dependence, narcotic action and dopamine receptors. Life Sci., 17, 483–496.CrossRefPubMedGoogle Scholar
  8. Neff, N.H., Parenti, M., Gentleman, S. and Olianas, M. (1981). Modulation of dopamine receptors by opiates. In Clinical Pharmacology of Apomorphine and Other Dopaminomimetics, (ed. G.U. Corsini), Raven Press, New York.Google Scholar
  9. Snyder, S.H., Pasternak, G. and Pert, C.B. (1975). Opiate receptor mechanisms. In Handbook of Psychopharmacology, Vol. 5, (eds. L. Iversen, S. Iversen and S.H. Snyder), Plenum Press, New York.Google Scholar
  10. Walczak, S.A., Wilkening, D. and Makman, M.H. (1979). Interaction of morphine, etorphine and enkephalins with dopaminestimulated adenylate cyclase in monkey amygdala. Brain Res. 160, 105–116.CrossRefPubMedGoogle Scholar

Copyright information

© The Contributors 1981

Authors and Affiliations

  • Susan Gentleman
    • 1
  1. 1.Section on Biochemistry and Pharmacology, Biological Psychiatry BranchNational Institute of Mental HealthBethesdaUSA

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