Uncoupling of the platelet alpha 2-adrenoceptor adenylate cyclase system by N-ethylmaleimide and the resulting effect on receptor density and sensitivity.
Preincubation of platelet-rich plasma with N-ethylmaleimide (NEM) attenuated the inhibitory effect of the alpha 2-adrenoceptor agonist UK 14304 on basal and forskolin-stimulated adenylate cyclase activities. NEM also led to concomitant marked reductions of the specific binding of [3H]UK 14304 to platelet membranes and of the primary aggregation response induced by UK 14304. These results indicate that uncoupling of the receptor adenylate cyclase system by NEM induces down-regulation of platelet alpha 2-adrenoceptor density (3H-agonist binding sites) and of the associated functional response (platelet aggregation).
García-Sevilla
J A
JA
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Spain.
Areso
P
P
Giralt
M T
MT
Ulibarri
I
I
D000262:Adenylyl Cyclases / Q000097:blood*; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D005576:Colforsin / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000959:Antihypertensive Agents; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D013439:Sulfhydryl Reagents; D005576:Colforsin; D000068438:Brimonidine Tartrate; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide