[Study of the signal transduction system of platelet alpha 2-adrenergic receptors in endogenous depression].

Abstract

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)

• Authors: H Mori
• Journal: [Hokkaido igaku zasshi] The Hokkaido journal of medical science (Hokkaido Igaku Zasshi) Vol. 67 Issue 2 Pg. 191-9 (Mar 1992) ISSN: 0367-6102 [Print] Japan
• PMID: 1350770 (Publication Type: English Abstract, Journal Article)

Chemical References

• Adrenergic alpha-Antagonists
• Receptors, Adrenergic, alpha
• Epinephrine

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Adult
• Aged
• Blood Platelets (metabolism)
• Depression (metabolism)
• Epinephrine (pharmacology)
• Female
• Humans
• Male
• Middle Aged
• Receptors, Adrenergic, alpha (physiology)
• Signal Transduction (drug effects)