Differential effects of Ro 20-1724 and isobutylmethylxanthine on the basal force of contraction and beta-adrenoceptor-mediated response in the rat ventricular myocardium.
Effects of Ro 20-1724, a selective inhibitor of soluble cGMP-insensitive type IV phosphodiesterase, on the force and cAMP levels were compared with those of 3-isobutyl-1-methylaxanthine, a non-selective inhibitor, in the rat ventricular myocardium. Ro 20-1724 scarcely affected the basal force of contraction and cAMP levels, whereas it enhanced the positive intropic effect and cAMP accumulation induced by isoproterenol more effectively than 3-isobutyl-1-methylxanthine. These results imply that inhibition of the soluble cGMP-insensitive type IV PDE by Ro 20-1724 may be crucially involved in the regulation of myocardial contractility through the interaction with cAMP generation in the rat ventricular myocardium.
Katano
Y
Y
Department of Pharmacology, Yamagata University School of Medicine, Japan.
Endoh
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives*
D007093:Imidazoles; D007527:Isoenzymes; D011943:Receptors, Adrenergic, beta; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D013806:Theophylline; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine