Alpha 2-adrenoceptor-mediated inhibition of platelet adenylate cyclase and induction of aggregation in major depression. Effect of long-term cyclic antidepressant drug treatment.
The functional status of platelet alpha 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 alpha 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 alpha 2-adrenoceptor activation. alpha 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.
García-Sevilla
J A
JA
Department of Pharmacology, University of the Basque Country Medical School, Vizcaya, Spain.
Padró
D
D
Giralt
M T
MT
Guimón
J
J
Areso
P
P
D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D000068438:Brimonidine Tartrate; D005576:Colforsin / Q000494:pharmacology; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists; D000929:Antidepressive Agents, Tricyclic; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D000068438:Brimonidine Tartrate; D004837:Epinephrine