Possible involvement of prostaglandins F(2alpha) and D(2) in acetylcholine-induced positive inotropy in isolated mouse left atria.
The inotropic action of prostaglandins PGF(2alpha), PGD(2) and PGE(2) on isolated mouse left atria was characterized and compared with the positive inotropic action of acetylcholine, which has previously been shown to be mediated by prostaglandins released from the endocardial endothelium. PGF(2alpha), PGD(2) and PGE(2) produced positive inotropic responses; the time course of the change in contractile force induced by PGF(2alpha) and PGD(2) was about the same as that by acetylcholine, while that by PGE(2) was slower. Fluprostenol and sulprostone, FP and EP receptor agonists, respectively, had positive inotropic effects while BW-245C, a DP receptor agonist, had no effect. AH-6809, a DP receptor antagonist, had no inhibitory effect on the positive inotropic response to PGD(2). Dimethylamiloride, an inhibitor of Na(+)/H(+) exchange, inhibited the positive inotropic response to PGF(2alpha), PGD(2) and acetylcholine, but not PGE(2). Fluorometric pH measurement with carboxy-SNARF-1-loaded atrial myocytes revealed no change in intracellular pH on application of PGF(2alpha). PGF(2alpha) and PGD(2) significantly prolonged the duration of the atrial action potential while PGE(2) had no significant effect. These findings suggest that prostaglandins induce positive inotropic response in mouse atria through FP and EP receptor stimulation and that the former mechanism mediates in part the positive inotropic response to acetylcholine.
Tanaka
Hikaru
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan. htanaka@phar.toho-u.ac.jp
Nishimaru
Kazuhide
K
Makuta
Ryuji
R
Hirayama
Wataru
W
Kawamura
Taro
T
Matsuda
Tomoyuki
T
Tanaka
Yoshio
Y
Kawanishi
Toru
T
Shigenobu
Koki
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000819:agonists; D013268:Stimulation, Chemical; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D011448:Prostaglandin Antagonists; D011982:Receptors, Prostaglandin; D014665:Vasodilator Agents; D015237:Dinoprost; D015230:Prostaglandin D2