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Effects of α 2 ‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets
Author(s) -
Clare Katherine A.,
Scrutton Michael C.,
Thompson Neil T.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10782.x
Subject(s) - cyclase , adenylate kinase , chemistry , agonist , antagonist , endocrinology , medicine , biochemistry , stereochemistry , receptor , biology
1 A range of 2–(,5‐dihydroimidazolyl)‐benzene, ‐quinoline, and ‐quinoxaline derivatives and 2‐morpholino‐4‐catechol have been characterized as agonists or partial agonists for human platelet aggregation; and for inhibition of adenylate cyclase by measurement of their effect on platelet [cyclic‐3′,5′‐AMP]. Antagonist activity for these compounds versus adrenaline as agonist has also been assessed for these two responses. 2 The compounds can be divided into 4 groups. Group I contains compounds that are agonists for both responses; group II, compounds that are agonists for inhibition of adenylate cyclase but antagonists for the aggregatory response; group III, compounds that are agonists for the aggregatory response but are antagonists for inhibition of adenylate cyclase by adrenaline; and group IV, compounds that are antagonists for both responses. 3 In group I the EC 50 values for induction of aggregation are not significantly different from the EC 50 values for inhibition of adenylate cyclase except for 2‐morpholino‐4‐catechol which is significantly more potent as an inhibitor of adenylate cyclase. 4 In group IV a linear correlation is observed between the K 1 values for the two responses for 8 compounds but 2 other compounds do not conform to this correlation. 5 The data are not consistent with a model in which a single x 2 ‐adrenoceptor mediates both the aggregatory response and inhibition of adenylate cyclase and hence support a model in which unique x 2 ‐adrenoceptors mediate these two responses.