Biogenic Amine-Stimulated Adenylate Cyclase and Spiroperidol-Binding Sites in Rabbit Brain: Evidence for Selective Loss of Receptors with Aging

  • M. H. Makman
  • H. S. Ahn
  • L. J. Thal
  • B. Dvorkin
  • S. G. Horowitz
  • N. S. Sharpless
  • M. Rosenfeld
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 113)


The aging process in man results in or is accompanied by a host of changes in brain structure and biochemistry (Terry and Gershon, 1976). The possible relationship of these alterations to the diminished mental function seen frequently in the older population is not yet known. Furthermore, the implications of these alterations for the manifestation and severity of neurological diseases such as parkinsonism are poorly understood. A major task in the investigation of biochemical changes occurring with senescence is to sort out the early or primary changes of greatest functional significance. In this regard, it is becoming increasingly evident that biogenic amine and closely interrelated transmitter or synaptic modulator systems play important roles in hypothalamic, cortical and extrapyramidal system functions. A number of studies have indicated that in experimental animals and in man deficiencies in brain aminergic systems, assessed functionally and/or biochemically, may occur with senescence (Finoh, 1973; Finch, Jonec, Hody, Walker, Morton-Smith, Alper and Dougher, 1975; Jonec and Finch, 1975; McGeer and McGeer, 1976ab; McGeer, McGeer and Suzuki, 1977; Simpkins, Mueller, Huang and Meites, 1977) (see also Finch and McGeer in this volume).


Frontal Cortex Dopamine Receptor Adenylate Cyclase Biogenic Amine Cyclase Activity 
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  1. Ahn, H.S. and Makman, M.H. (1977). Neurotransmitter-sensitive adenylate cyclase in the hypothalami of guinea-pig, rat and monkey. Brain Res. 138, 125–138.PubMedCrossRefGoogle Scholar
  2. Ahn, H.S., Mishra, R.K., Demirjian, C. and Makman, M.H. (1976). Cathecholamine-sensitive adenylate cyclase in frontal cortex of primate brain. Brain Res. 116, 437–454.PubMedCrossRefGoogle Scholar
  3. Brockaert, J., Tassin, J.P., Thierry, A.M., Glowinski, J. and Premont, J. (1977). Characteristics of dopamine and ß-adrenergic sensitive adenylate cyclases in the frontal cerebral cortex of the rat. Comparative effects of neuroleptics on frontal cortex and striatal dopamine sensitive adenylate cyclases. Brain Res. 122, 71–86.CrossRefGoogle Scholar
  4. Brown, J.H. and Makman, M.H. (1972). Stimulation by dopamine of adenylate cyclase in retinal homogenates and of adenosine-3′5′ cyclic AMP formation in intact retina. Proc. natn. Acad. Soi. 69, 539–543.CrossRefGoogle Scholar
  5. Brown, J.H. and Makman, M.H. (1973). Influence of neuroleptic drugs and apomorphine on dopamine-sensitive adenylate cyclase of retina. J. Neurochem. 21, 477–479.PubMedCrossRefGoogle Scholar
  6. Burt, D.R., Creese, I. and Snyder, S.J. (1976). Properties of [3H]haloperidol and [3H] dopamine binding associated with dopamine receptors in calf brain membranes. Mol. Pharmac. 12, 800–812.Google Scholar
  7. Creese, I., Burt, D.R. and Snyder, S.H. (1975). Dopamine receptor binding differentiation of agonist and antagonist states with 3H-dopamine and 3H-haloperidol. Life Sci. 17, 993–1002.CrossRefGoogle Scholar
  8. Creese, I., Burt, D.R. and Snyder, S.H. (1977). Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197, 596–598.PubMedCrossRefGoogle Scholar
  9. Datta, K., Thal, L. and Wajda, I. (1971). Effects of morphine on choline acetyltransferase levels in the caudate nucleus of the rat. Br. J. Pharmac. 41, 84–93.CrossRefGoogle Scholar
  10. Fields, J.Z., Reisine, T.D. and Yamamura, H.I. (1978). Biochemical demonstration of dopaminergic receptors in rat and human brain using 3H-spiroperidol. Brain Res. (In Press).Google Scholar
  11. Finch, C.E. (1973). Catecholamine metabolism in the brains of aging male mice. Brain Res. 52, 261–276.PubMedCrossRefGoogle Scholar
  12. Finch, C.E., Jonec, V., Hody, G., Walker, J.P., Morton-Smith, W., Alper, A. and Dougher, G.J., Jr. (1975). Aging and the passage of L-tyrosine, L-DOPA, and insulin into mouse brain slices in vitro. J. Geront. 30, 33–40.PubMedCrossRefGoogle Scholar
  13. Höllt, V., Czlonkowski, A. and Herz, A. (1977). The demonstration in vivo of specific binding sites for neuroleptic drugs in mouse brain. Brain Res. 130, 176–183.PubMedCrossRefGoogle Scholar
  14. Iversen, L. (1975). Dopamine receptors in the brain: a dopamine-sensitive adenylate cyclase models synaptic receptors, illuminating antipsychotic drug action. Science 188, 1084–1089.PubMedCrossRefGoogle Scholar
  15. Jonec, V.J. and Finch, C.E. (1975). Aging and dopamine uptake by subcellular fractions of the C57BL/6J male mouse brain. Brain Res. 91, 197–215.PubMedCrossRefGoogle Scholar
  16. Kakiuchi, S. and Rall, T.W. (1968). The influence of chemical agents on the accumulation of adenosine 3, ‘5’-phosphate in slices of rabbit cerebellum. Mol. Pharmac. 4, 367–378.Google Scholar
  17. Kebabian, J.W., Petzold, G.L. and Greengard, P. (1972). Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptor”. Proc. natn. Acad. Sci. 69, 2145–2149.CrossRefGoogle Scholar
  18. Laduron, P.M., Janssen, P.F.M. and Leysen, J. (1978). Spiperone: a ligand of choice for neuroleptic receptors. 2. Regional distribution and in vivo displacement of neuroleptic drugs. Biochem. Pharmac. 27, 317–321.CrossRefGoogle Scholar
  19. McGeer, P.L. and McGeer, E.G. (1976a). Enzymes associated with the metabolism of catecholamines, acetylcholine and GABA in human controls and patients with Parkinson’s disease and Huntington’s chorea. J. Neurochem. 26, 65–76.PubMedGoogle Scholar
  20. McGeer, E.G. and McGeer, P.L. (1976b). In: Neurobiology of Aging, vol. 3, pp. 389–403. Eds. R. Terry and S. Gershon. Academic Press, New York.Google Scholar
  21. McGeer, P.L., McGeer, E.G. and Suzuki, J.S., (1977). Aging and extrapyramidal function. Arch. Neurol. 34, 33–35.PubMedCrossRefGoogle Scholar
  22. Makman, M.H. (1971). Properties of adenylate cyclase of lymphoid cells. Proc. natn. Acad. Sci. 68, 885–889.CrossRefGoogle Scholar
  23. Makman, M.H. (1977). Actions of cyclic AMP and its relationship to transmitter function in nervous tissue. In: Biochemical Actions of Hormones, vol 4, pp. 407–496. Ed. G. Litwack. Academic Press, New York.CrossRefGoogle Scholar
  24. Makman, M.H., Brown, J.H. and Mishra, R.K. (1975). Cyclic AMP in retina and caudate nucleus: influence of dopamine and other agents. Adv. Cyc. Nucleo. Res. 5, 661–679.Google Scholar
  25. Makman, J.H., Morris, S.A. and Ahn, H.S. (1977). Cyclic nucleotides. In: Growth, Nutrition and Metabolism of Cells in Culture, vol. 3, pp. 295–354. Eds. G.H. Rothblat and V.J. Cristofalo. Adacemic Press, New York.Google Scholar
  26. Makman, M.H., Ahn, H.S., Thal, L., Dvorkin, B., Horowitz, S.G., Sharpless, N. and Rosenfeld, M. (1978). Decreased brain biogenic amine-stimulated adenylate cyclase and and spiro-peridol-binding sites with aging. Fed. Proc. 37, 548.Google Scholar
  27. Mishra, R.K., Gardner, E.L., Katzman, R. and Makman, M.H. (1974). Enhancement of dopamine-stimulated adenylate cyclase activity in rat caudate after lesions in substantia nigra: evidence for denervation supersensitivity. Proc. natn. Acad. Sci. 71, 3883–3887.CrossRefGoogle Scholar
  28. Mishra, R.K., Makman, M.H., Ahn, H.S., Dvorkin, B., Horowitz, S.G., Keehn, E. and Demirjian, C. (1976). Differences in primate brain regions in relative potency for antagonism of dopamine-stimulated adenylate cyclases by neuroleptic drugs and possible implications for localization of antipsychotic activity. Neurosci. Abst. 2, 1134.Google Scholar
  29. Puri, S.K. and Volicer, L. (1977). Effect of aging on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in the rat corpus striatum. Mech. Aging. Dev. 6, 53–58.PubMedCrossRefGoogle Scholar
  30. Schocken, D.D. and Roth, G.S. (1977). Reduced β-adrenergic receptor concentrations in aging man. Nature 267, 856–858.PubMedCrossRefGoogle Scholar
  31. Sharpless, N.S. and Brown, L.L. (1978). Use of microwave irradiation to prevent post-mortem catecholamine metabolism: evidence for tissue disruption artifact in a discrete region of rat brain. Brain Res. 140, 171–176.PubMedCrossRefGoogle Scholar
  32. Simpkins, J.W., Mueller, G.P., Huang, H.H. and Meites, J. (1977). Evidence for depressed catecholamine and enhanced serotonin metabolism in aging male rats: possible relation to gonadotropin secretion. Endocrinology 100, 1672–1678.PubMedCrossRefGoogle Scholar
  33. Snyder, S.H. and Bennett, J.P., (1976). Neurotransmitter receptors in the brain: biochemical identification. A. Rev. Physiol. 38, 153–175.CrossRefGoogle Scholar
  34. Spiker, M.D., Palmer, G.C. and Manian, A.A. (1976). Action of neuroleptic agents on histamine-sensitive adenylate cyclase in rabbit cerebral cortex. Brain Res. 104, 401–406.PubMedCrossRefGoogle Scholar
  35. Terry, R.D. and Gershon, S. (1976). Neurobiology of Aging. Academic Press, New York.Google Scholar
  36. Wilkening, D. and Makman, M.H. (1975). 2-Chloroadenosine-dependent elevation of adenosine 3′, 5′-cyclic monophosphate levels in rat caudate nucleus slices. Brain Res. 92, 522–528.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • M. H. Makman
    • 1
    • 2
  • H. S. Ahn
    • 3
  • L. J. Thal
    • 3
  • B. Dvorkin
    • 1
  • S. G. Horowitz
    • 1
  • N. S. Sharpless
    • 4
  • M. Rosenfeld
    • 2
  1. 1.Department of BiochemistryAlbert Einstein College of MedicineNew YorkUSA
  2. 2.Department of Molecular PharmacologyAlbert Einstein College of MedicineNew YorkUSA
  3. 3.Department of NeurologyAlbert Einstein College of MedicineNew YorkUSA
  4. 4.Department of PsychiatryAlbert Einstein College of MedicineNew YorkUSA

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