Study of the signal transduction system of platelet alpha 2-adrenergic receptors in endogenous depression
Mori, H.
Hokkaido Journal of Medical Science 67(2): 191-199
1992
ISSN/ISBN: 0367-6102 PMID: 1350770 Document Number: 400438
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.