[Study of the signal transduction system of platelet alpha 2-adrenergic receptors in endogenous depression].
Researches in the mechanisms of action of antidepressant drugs have recently suggested that endogenous depression is related to an altered sensitivity of alpha-2 adrenergic receptors. Since this hypothesis is difficult to study in the central nervous system of human subjects directly, the alpha-2 adrenergic receptors on peripheral-blood platelets have been used as an accessible and convenient marker of the receptor function. Although the inhibition of adenylate cyclase, via the GTP-binding protein termed Gi, was believed to be the exclusive mechanism of alpha-2 adrenergic receptor action in the platelet, this concept has become less tenable. We have recently indicated that epinephrine stimulates phosphoinositide (PI) hydrolysis by activating alpha-2 adrenergic receptors in human platelets [Life Sci., 741-747 44 (1989)]. This method involves the measurement of the accumulation of [3H] -inositol-1-phosphate (IP-1) as an index of PI hydrolysis; lithium is added to inhibit the metabolism of IP-1, thus giving an enhanced signal. In addition, this PI response elicited by epinephrine was found to be inhibited in a concentration-dependent manner by treatment of platelets with dibutyryl cyclic AMP and 8-bromo-cyclic GMP which are known as potent inhibitors for platelet activation, and may therefore be a useful biochemical index for the study of the signal transduction system of alpha -2 adrenergic receptors. In the present study, the platelet alpha-2 adrenergic receptor-mediated PI responses were assessed in 15 unmedicated patients with endogenous depression and 15 age -and sex-matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D004837:Epinephrine