Neurochemical Research

, Volume 7, Issue 1, pp 115–124 | Cite as

The dopamine receptor adenylate cyclase complex: Evidence for post recognition site involvement for the development of supersensitivity

  • M. Parenti
  • S. Gentleman
  • M. C. Olianas
  • N. H. Neff
Original Articles


The dopamine receptor adenylate cyclase complex of a rat striatal membrane preparation became more responsive to dopamine following the injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle or following the subcutaneous implantation of morphine pellets. Moreover, the membrane cyclase system was more responsive to activation by GTP, guanyl-5′-yl-imidodiphosphate and Mn-ATP. These observations suggest that both 6-OHDA and morphine induce similar biochemical changes in striatum and that the increased responsiveness arises, in part, from modification of the nucleotide regulatory and/or catalytic components of adenylate cyclase.


Nucleotide Dopamine Morphine Adenylate Cyclase Recognition Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Gnegy, M. E., andCosta, E. 1980. Catecholamine receptor supersensitivity and subsensitivity in the central nervous systems. Pages 249–282,in Youdim, M. B. H., Lovenberg, W., Sharman, D. F., andLagnado, J. R. (eds.), Essays in Neurochemistry and Neuropharmacology, John Wiley and Sons, England.Google Scholar
  2. 2.
    Schwartz, J. C., Costentin, J., Martres, M. P., Protais, P., andBaudry, M. 1978. Modulation of receptor mechanisms in the CNS: Hyper- and hyposensitivity to catecholamines. Neuropharmacology 17:665–685.Google Scholar
  3. 3.
    Dismukes, R. K., andDaly, J. W. 1976. Adaptive responses of brain cyclic AMP-generating systems to alterations in synaptic input. J. Cyclic Nucleotide Res. 2:321–336.Google Scholar
  4. 4.
    Mishra, R. K., Gardner, E. L., Katzman, R., andMakman, M. H. 1974. Enhancement of dopamine-stimulated adenylate cyclase activity in rat caudate after lesions in the substantia nigra: Evidence for denervation supersensitivity. Proc. Natl. Acad. Sci. (Wash.) 71:3883–3887.Google Scholar
  5. 5.
    Lal, H. 1975. Narcotic dependence, narcotic action and dopamine receptors. Life Sci. 17:483–495.Google Scholar
  6. 6.
    Gentleman, S., Parenti, M., Commissiong, J. W., andNeff, N. H. 1981. Dopamine-activated adenylate cyclase of spinal cord: Supersensitivity following transection of the cord. Brain Res. 210:271–275.Google Scholar
  7. 7.
    Salomon, Y., Londons, C., andRodbell, M. 1974. A highly sensitive adenylate cyclase assay. Anal. Biochem. 58:541–548.Google Scholar
  8. 8.
    Ungerstedt, U. 1971. Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system in the rat brain. Acta Physiol. Scand. Suppl. 82:69–93.Google Scholar
  9. 9.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., andRandall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.Google Scholar
  10. 10.
    Weimer, G., Kaiser, G., andPalm, D. 1978. Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity: Evidence for a metallic site. Naunyn-Schmiedebergs Arch. Pharmacol. 303:145–152.Google Scholar
  11. 11.
    Creese, I., Burt, D. R., andSnyder, S. H. 1977. Dopamine receptor binding enhancement accompanies lesion-induced behavioural supersensitivity. Science 197:596–598.Google Scholar
  12. 12.
    Collier, H. O. J., andRoy, A. C. 1974. Morphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenate. Nature 248:24–27.Google Scholar
  13. 13.
    Walczak, S. A., Wilkening, D., andMakman, M. H. 1979. Interaction of morphine, etorphine and enkephalins with dopamine-stimulated adenylate cyclase of monkey amygdala. Brain Res. 160:105–116.Google Scholar
  14. 14.
    Sharma, S. K., Klee, W. A., andNirenberg, M. 1977. Endorphin from pituitary inhibits cyclic AMP formation in homogenates of neuroblastoma x glioma hybrid cells. Nature 265:362–363.Google Scholar
  15. 15.
    Minneman, K. P., andIversen, L. L. 1976. Enkephalin and opiate narcotics increase cyclic GMP accumulation in slices of rat neostriatum. Nature 262:313–314.Google Scholar
  16. 16.
    Blume, A. J., Lichtshtein, D., andBoone, G. 1979. Coupling of opiate receptors to adenylate cyclase: Requirement for Na+ and GTP. Proc. Natl. Acad. Sci. (Wash.) 76:5626–5630.Google Scholar
  17. 17.
    Cooper, D. M. F., Schlegel, W., Lin, M. C., andRodbell, M. 1979. The fat cell adenylate cyclase system: Characterization and manipulation of its bimodal regulation by GTP. J. Biol. Chem. 254:8927–8931.Google Scholar
  18. 18.
    Steer, M. L., andWood, A. 1979. Regulation of human platelet adenylate cyclase by epinephrine, prostaglandin E1 and guanine nucleotides. J. Biol. Chem. 254:10791–10797.Google Scholar
  19. 19.
    Rodbell, M., Lin, M. C., Salomon, Y., Londos, C., Harwood, J. P., Martin, B. R., Rendell, M., andBerman, M. 1975. Role of adenine and guanine nucleotides in the activity and response of adenylate cyclase systems to hormones: Evidence for multisite transition states. Adv. Cyclic Nucleotide Res. 5:3–30.Google Scholar
  20. 20.
    Pike, L. J., Limbird, L. E., andLefkowitz, R. J. 1979. β-Adrenoreceptors determine affinity but not intrinsic activity of adenylate cyclase stimulants. Nature 280:502–504.Google Scholar
  21. 21.
    Childers, S. R., andSnyder, S. H. 1980. Characterization of [3H]guanine nucleotide binding sites in brain membranes. J. Neurochem. 25:183–192.Google Scholar

Copyright information

© Plenum Publishing Corporation 1982

Authors and Affiliations

  • M. Parenti
    • 1
  • S. Gentleman
    • 1
  • M. C. Olianas
    • 1
  • N. H. Neff
    • 1
  1. 1.Laboratory of Preclinical Pharmacology National Institute of Mental HealthSaint Elizabeths HospitalWashington, D.C.

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