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Carbamylcholine inhibits β‐adrenergic receptor‐coupled G s protein function proximal to adenylate cyclase
Author(s) -
Avissar Sofia,
Schreiber Gabriel
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80075-t
Subject(s) - g protein , adenylate kinase , cholera toxin , pertussis toxin , cyclase , gs alpha subunit , chemistry , gi alpha subunit , gtp' , agonist , g alpha subunit , guanosine , biochemistry , protein subunit , receptor , biology , endocrinology , gene , enzyme
The specific mechanism by which the inhibitory guanine nucleotide binding protein (G i ) mediates the inhibition of adenylate cyclase activity is still unclear. The subunit dissociation model, based on studies in purified or reconstituted systems, suggests that the βγ subunit, which is dissociated with activation of G i , inhibits the function of the stimulatory guanine nucleotide binding protein (G s ) by reducing the concentration of the free α s subunit. In the present study, G s , protein function is determined by measuring cholera toxin‐blockable, isoproterenol‐induced increases in guanosine triphosphate (GTP) binding capacity to rat cardiac ventricle membrane preparations. Carbamylcholine totally inhibited this β‐adrenergic receptor‐coupled G s protein function. Pretreatment of the cardiac ventricle membrane preparation with pertussis toxin prevented this muscarinic agonist effect. These results confirm the possibility of an inhibitory agonist‐receptor coupled effect through G i on G s protein function proximal to the catalytic unit of adenylate cyclase in an intact membrane preparation.