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 2-Adrenoceptor—Mediated Inhibition of Platelet Adenylate Cyclase and Induction of Aggregation in Major DepressionEffect of Long-term Cyclic Antidepressant Drug Treatment
Jesus A. Garcia-Sevilla, MD;
Daniel Pardro, MD;
M. Teresa Giralt, PhD;
Jose Guimon, MD;
Pilar Areso, PhD
Arch Gen Psychiatry. 1990;47(2):125-132.
Abstract
• The functional status of platelet  2-adrenoceptors in patients with major depression has been assessed by simultaneously measuring both a biochemical mechanism of transduction of receptor activation (inhibition of adenylate cyclase activity) and a physiologic response of the receptor (induction of aggregation). The inhibitory effects induced by epinephrine and UK 14304 on adenylate cyclase activity were unchanged, while the aggregation responses induced by the same 2-adrenoceptor agonists were potentiated, which indicated receptor supersensitivity. In depressed (n 30) and euthymic (n = 11) patients as well as in control subjects (n = 66), there was a clear dissociation between inhibition of adenylate cyclase activity and induction of aggregation, indicating that the two responses represent different phenomena of 2-adrenoceptor activation. 2-Adrenoceptor-mediated platelet aggregation could represent a better marker than inhibition of adenylate cyclase to assess functional changes of the receptor in depression. Both of these functional responses are desensitized after long-term antidepressant treatment.
Author Affiliations
From the Departments of Pharmacology (Drs Garacia-Sevilla, Giralt, and Areso) and Psychiatry (Drs Padro and Guimon), University of the Basque Country Medical School, Vizcaya, Spain. Dr Garcia-Sevilla is now with the Department of Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain.
Footnotes
Accepted for publication July 10, 1989.
Read in part at the Annual Meeting of the Spanish Pharmacological Society, Santander, Spain, September 24, 1986; at the International Conference on New Directions in Affective Disorders, Jerusalem, Israel, April 8, 1987; and at the Conference of the British Association for Psychopharmacology: Antidepressants—Thirty Years On, Galway, Ireland, September 16, 1988.
Reprint requests to Department of Biology and Health Sciences, University of the Balearic Islands, Ctra Valldemossa, Km 7.5, E-07071 Palma de Mallorca, Spain (Dr Garcia-Sevilla).
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