Stimulation of cyclic AMP-dependent protein kinase in rat atria by (-)-CGP 12177 through an atypical beta-adrenoceptor.
Mammalian hearts possess an atypical beta-adrenoceptor (non-beta 1, non-beta 2, non-beta 3) through which (-)-4-(3-t-butylamino-2 -hydroxypropoxy)benzimidazol-2-one ((-)-CGP 12177) causes cardiostimulant effects. Here we showed that (-)-CGP 12177 increased the activity of adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase in the presence of 200 nM (-)-propranolol in rat atria at a concentration (10 microM) that elicits maximum positive chronotropic and inotropic effects. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) potentiated the positive chronotropic and inotropic effects of (-)-CGP 12177. We suggest that the atypical beta-adrenoceptor is coupled positively to the Gs protein-adenylyl cyclase system.
Kaumann
A J
AJ
Babraham Institute, Human Pharmacology Laboratory, Cambridge.
Lynham
J A
JA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; C033394:CGP 12177; D015056:1-Methyl-3-isobutylxanthine