Diazepam reduces action potential duration in guinea-pig papillary muscle by a cAMP-dependent mechanism.
In this study, we have analyzed the role of cyclic AMP (cAMP) as the mediator of the decrease in action potential duration induced by diazepam. Diazepam (1-100 microM) reduced, in a dose-dependent manner, the duration of intracellular action potential recorded in the papillary muscle obtained from the right ventricle of the guinea pig heart. This effect was mimicked by the analog of cyclic AMP, 8-Br-cAMP (100 microM), but not by gamma-amino-butyric acid (GABA). Also, the selective antagonist of the benzodiazepine receptors, flumazenil did not modify the effect of diazepam. The diazepam-induced shortening of action potential duration was partially antagonized by the inhibitor of cAMP synthesis carbachol (1 microM) or the blocker of the cAMP-dependent protein kinase A, Rp-cAMP[S] (1 microM). These results indicate that cyclic AMP is involved in the diazepam-induced shortening of the action potential duration of the guinea pig papillary muscle.
Janvier
J J
JJ
Departamento de Fisiología y Farmacología, Facultad de Medicina, Murcia, Spain.
García-Estañ
J
J
Hernández
J
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003975:Diazepam / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003975:Diazepam