title: Reduced adenylyl cyclase inhibition by carbachol and GTP during acute myocardial ischaemia.
abstract: Acute myocardial ischaemia frequently is complicated by ventricular tachyarrhythmias. These arrhythmias are in part due to an increased susceptibility of myocardial cells to adenylyl cyclase stimulation by catecholamines [1]. As adenylyl cyclase underlies an endogenous dual regulation by stimulatory and inhibitory receptor systems, adenylyl cyclase stimulation can be counteracted by the activation of receptors like the muscarinic M2 receptor [2]. Therefore, the effect of myocardial ischaemia on muscarinic receptor and "inhibitory" guanine nucleotide binding proteins (G(i)) mediated inhibition of adenylyl cyclase was studied. During 5 min of myocardial ischaemia, carbachol mediated inhibition of forskolin and isoproterenol stimulated adenylyl cyclase was reduced by 30% and 50%, respectively. Hormone independent inhibition of adenylyl cyclase by the nonhydrolyzable GTP-analogue guanosine 5'-[beta gamma-imido]triphosphate (Gpp(NH)p) was reduced by 46%. In contrast, the amount of G(i), as determined by pertussis toxin catalyzed ADP-ribosylation, remained constant during 15 min of ischaemia. The impaired function of muscarinic receptor linked signal transduction during early myocardial ischaemia could contribute to the occurrence of ischaemia induced tachyarrhythmias by a reduced ability to counteract adenylyl cyclase activation.
authors.affiliation: Medizinische Klinik, Universität Heidelberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Niroomand
authors.forename: M
authors.initials: M
authors.lastname: Bangert
authors.forename: T
authors.initials: T
authors.lastname: Beyer
authors.forename: B
authors.initials: B
authors.lastname: Rauch
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000037:antagonists & inhibitors; D003327:Coronary Disease / Q000201:enzymology* / Q000503:physiopathology; D004285:Dogs; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D011976:Receptors, Muscarinic / Q000502:physiology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D011976:Receptors, Muscarinic; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D002217:Carbachol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol