Advertisement

Psychopharmacologia

, Volume 36, Issue 4, pp 291–300 | Cite as

Platelet adenylate cyclase responses in depression: Implications for a receptor defect

  • Yao -Chun Wang
  • Ghanshyam N. Pandey
  • Joe Mendels
  • Alan Frazer
Human Pharmacology
Received:
Revised:

Abstract

The dose-dependent stimulatory response of prostaglandin E1 (PGE1) on the net synthesis of 3H-adenosine 3′,5′-monophosphate (cyclic AMP) in platelets whose adenine nucleotide pools had been labelled by prior incubation with 3H-adenine was measured. Also, the dose-dependent inhibition produced by norepinephrine (NE) on this stimulatory process was evaluated. Platelets were obtained from eleven moderately depressed male patients and from eight non-depressed normal male control subjects. No difference was noted between the two groups of subjects either in the stimulation produced by PGE1 or in the inhibition caused by NE. Subdividing the patients into different subgroups (e.g., bipolar or unipolar) did not produce any significant differences. This finding suggests that there is no generalized defect in alpha adrenergic responses in depressed male patients.

Key words

Adenylate Cyclase Norepinephrine Prostaglandin E1 Platelet Depression 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdulla, Y. H., Hamadah, K.: 3′,5′-cyclic adenosine monophosphate in depression and mania. Lancet 1970I, 378–381Google Scholar
  2. Aschroft, G. W., Eccleston, D., Murray, L. G., Glen, A. I. M.: Modified amine hypothesis for the aetology of affective illness. Lancet 1972II, 573–577Google Scholar
  3. Beck, A. T., Ward, C. H., Mendelson, M. J., Erbaugh, J.: An inventory for measuring depression. Arch. gen. Psychiat. 4, 561–571 (1961)Google Scholar
  4. Brown, B. L., Salway, J. G., Albano, J. D. M., Hullin, R. P., Ekins, R. P.: Urinary excretion of cyclic AMP and manic-depressive psychosis. Brit. J. Psychiat. 120, 405–408 (1972)Google Scholar
  5. Carroll, B. J.: Monoamine precursors in the treatment of depression. Clin. Pharmacol. 12, 743–761 (1971)Google Scholar
  6. Chasin, M., Rivkin, I., Mamrak, F., Samaniego, S. G., Hess, S. M.: Alpha and beta-adrenergic receptors as mediators of accumulation of cyclic AMP in specific areas of guinea pig brain. J. biol. Chem. 246, 3037–3041 (1971)Google Scholar
  7. Coppen, A.: The biochemistry of affective disorders. Brit. J. Psychiat. 113, 1237–1264 (1967)Google Scholar
  8. Cramer, H., Goodwin, F. K., Post, R. M., Bunney, W. E.: Effects of probenecid and exercise on cerebrospinal fluid cyclic AMP in affective illness. Lancet 1972I, 1346–1347Google Scholar
  9. Hamilton, M.: A rating scale for depression. J. Neurol. Neurosurg. Psychiat. 23, 56–61 (1960)Google Scholar
  10. Jenner, F. A., Sampson, G. A., Thompson, E. A., Somerville, A. R., Beard, N. A., Smith, A. A.: Manic-depressive psychosis and urinary excretion of cyclic AMP. Brit. J. Psychiat. 121, 236–237 (1972)Google Scholar
  11. Kakiuchi, S., Rall, T. W.: The influence of chemical agents on the accumulation of cyclic AMP in slices of rabbit cerebellum. Molec. Pharmacol. 4, 367–378 (1968)Google Scholar
  12. Kakiuchi, S., Rall, T. W., McIlwain, H.: The effect of electrical stimulation upon the accumulation of adenosine 3′,5′-phosphate in isolated cerebral tissue. J. Neurochem. 16, 485–491 (1969)Google Scholar
  13. Krishna, G., Weiss, B., Brodie, B. B.: A simple, sensitive method for the assay of adenyl cyclase. J. Pharmacol. exp. Ther. 163, 379–385 (1968)Google Scholar
  14. Kuo, J. F., De Renzo, E. C.: A comparison of the effects of lipolytic and antilipolytic agents on adenosine 3′,5′-monophosphate levels in adipose cells as determined by prior labelling with adenine-814C. J. biol. Chem. 244, 2252–2260 (1969)Google Scholar
  15. Lindquist, E. F.: Design and Analysis, pp. 266–273. Boston: Houghton Mifflin Comp. 1956Google Scholar
  16. Marquis, N. R., Becker, J. A., Vigdahl, R. L.: Platelet aggregation. 3. An epinephrine induced decrease in cyclic AMP synthesis. Biochem. biophys. Res. Commun. 39, 783–789 (1970)Google Scholar
  17. Marshall, J. M.: Effects of catecholamines on the smooth muscle of the female reproductive tract. Ann. Rev. Pharmacol. 13, 19–32 (1973)Google Scholar
  18. Mendels, J., Stinnett, J. L.: Biogenic Amine Metabolism, Depression and Mania. In: Biological Psychiatry. J. Mendels, Ed., pp. 65–89. New York: John Wiley and Sons 1973Google Scholar
  19. Paul, M. I., Ditzion, B. R., Pauk, G. L., Janowsky, D. S.: Urinary adenosine 3′,5′-monophosphate excretion in affective disorders. Amer. J. Psychiat. 126, 1493–1497 (1970)Google Scholar
  20. Paul, M. I., Cramer, H., Goodwin, F. K.: Urinary cyclic AMP excretion in depression and mania. Effects of levodopa and lithium carbonate. Arch. gen. Psychiat. 24, 327–333 (1971)Google Scholar
  21. Perkins, J. P., Moore, M. M.: Characterization of the adrenergic receptors mediating a rise in cyclic 3′,5′-adenosine monophosphate in rat cerebral cortex. J. Pharmacol. exp. Ther. 185, 371–378 (1973)Google Scholar
  22. Post, R. M., Kotin, J., Goodwin, F. K., Gordon, E. K.: Psychomotor activity and cerebrospinal fluid amine metabolites in affective illness. Amer. J. Psychiat. 130, 67–72 (1973)Google Scholar
  23. Prange, A. J.: The pharmacology and biochemistry of depression. Dis. nerv. Syst. 25, 217–221 (1964)Google Scholar
  24. Prange, A. J., McCurdy, R. L., Cochrane, C. M.: The systolic blood pressure response of depressed patients to infused norepinephrine. J. psychiat. Res. 5, 1–13 (1967)Google Scholar
  25. Prange, A. J., Wilson, I. C., Rabon, A. M., Lipton, M. A.: Enhancement of imipramine antidepressant activity by thyroid hormone. Amer. J. Psychiat. 126, 457–469 (1969)Google Scholar
  26. Prange, A. J., Wilson, I. C., Knox, A., McClane, T. K., Lipton, M. A.: Enhancement of imipramine by thyroid stimulating hormone: Clinical and theoretical implications. Amer. J. Psychiat. 127, 191–199 (1970)Google Scholar
  27. Prange, A. J., Wilson, I. C., Knox, A. E., McClane, T. K., Breese, G. R., Martin, B. R., Alltop, L. B., Lipton, M. A.: Thyroidimipramine clinical and chemical interaction: Evidence for a receptor deficit in depression. J. psychiat. Res. 9, 187–205 (1972)Google Scholar
  28. Robins, E., Hartman, B. K.: Some Chemical Theories of Mental Disorders. In: Basic Neurochemistry. R. W. Albers et al., Eds., pp. 607–644. Boston: Little Brown and Comp. 1972Google Scholar
  29. Robison, G. A., Arnold, A., Hartman, R. C.: Divergent effects of epinephrine and prostaglandin E1 on the level of cyclic AMP in human blood platelets. Pharm. Res. Comm. 1, 325–332 (1969a)Google Scholar
  30. Robison, G. A., Butcher, R. W., Sutherland, E. W.: On the Relation of Hormone Receptors to Adenyl Cyclase. In: Fundamental Concepts in Drug-Receptor Interactions. Danielli et al., Eds. New York: Academic Press 1969bGoogle Scholar
  31. Robison, G. A., Coppen, A. J., Whybrow, P. C., Prange, A. J.: Affective disorders. Lancet 1970II, 1028–1029Google Scholar
  32. Schildkraut, J. J.: The catecholamine hypothesis of affective disorders. A review of supporting evidence. Amer. J. Psychiat. 122, 509–522 (1965)Google Scholar
  33. Shimizu, H., Daly, J. W., Creveling, C. R.: A radioisotopic method for measuring the formation of adenosine 3′,5′-monophosphate in incubated slices of brain. J. Neurochem. 16, 1609–1619 (1969)Google Scholar
  34. Shimizu, H., Tanaka, S., Suzuki, T., Matsukado, Y.: The response of human cerebrum adenyl cyclase to biogenic amines. J. Neurochem. 18, 1157–1161 (1971)Google Scholar
  35. Siggins, G. R., Hoffer, B. J., Bloom, F. E.: Cyclic AMP: Possible mediator for norepinephrine effects on cerebellar Purkinje cells. Science 165, 1018–1020 (1969)Google Scholar
  36. Snedecor, G. W.: Statistical Methods, 5th ed. Ames, Iowa: Iowa State College Press 1956Google Scholar
  37. Sutherland, E. W., Rall, T. W.: The relation of adenosine-3′,5′-monophosphate and phosphorylase to the action of catecholamines and other hormones. Pharmacol. Rev. 12, 265–299 (1960)Google Scholar
  38. Wang, Y.-C., Pandey, G. N., Mendels, J., Frazer, A.: The effect of lithium on prostaglandin E1-stimulated adenylate cyclase activity of human platelets. Biochem. Pharmacol. 23, 845–855 (1974)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • Yao -Chun Wang
    • 1
  • Ghanshyam N. Pandey
    • 2
  • Joe Mendels
    • 1
    • 2
  • Alan Frazer
    • 1
    • 2
  1. 1.Departments of Pharmacology and PsychiatryUniversity of Pennsylvania School of MedicinePhiladelphia
  2. 2.Affective Diseases Research UnitVeterans Administration HospitalPhiladelphia

Personalised recommendations

Cite article

Buy options