Pharmacology of peripheral type benzodiazepine receptors in the heart.
RO5-4864 decreased in a dose-dependent manner the duration of intra cellular action potential and the contractility in the guinea pig papillary muscle. Diazepam was less active and clonazepam inactive. The effects of RO5-4864 were blocked by PK 11195 but not by RO15-1788. These results indicate that peripheral type benzodiazepine binding sites are pharmacological receptors. PK 11195 antagonized the increase and the decrease in the duration of intracellular action potential induced by BAY K-8644 and calcium channel blockers (nitrendipine, diltiazem, verapamil) respectively but not the increase induced by tetraethylammonium which blocks potassium channel. Moreover the decrease in contractility provoked by RO5-4864 was antagonized by 4 mM Ca2+. Thus peripheral type BZ receptors are coupled with Ca2+ channels in the heart.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D016276:Ventricular Function
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195