Further studies on the potent positive chronotropic effect of (15S)-15-methyl-prostaglandin E1 on the guinea-pig isolated spontaneously beating right atrium.
1. 15-Me-PGE1 (10(-14)-10(-11) M) elicited a concentration-dependent and long-lasting increase in heart rate without an effect on contractility of the isolated spontaneously beating guinea-pig right atria. 2. Noradrenaline, histamine and PGE1 produced a concentration-dependent increase in both heart rate and contractility with relatively higher concentrations. 3. beta-Adrenoceptor blocker propranolol and histamine H2-receptor blocker cimetidine inhibited the effects of noradrenaline and histamine respectively without altering the positive chronotropic effect of 15-Me-PGE1. 4. Prazosin and lidocaine partially inhibited the effect of 15-Me-PGE1, while reducing Na+ concentration in the medium to 50 mM almost completely inhibited the positive chronotropic effect of the analog. 5. Calcium channel blocker, nicardipine, decreased the positive chronotropic effect of 15-Me-PGE1 in a concentration-dependent manner. 6. These results were taken as an evidence for the specific and unique effect of 15-Me-PGE1 in the guinea-pig sinoatrial node interacting with Na+ and Ca2+ fluxes probably through their specific exchangers.
Serdar Soydan
A
A
Department of Pharmacology, Faculty of Medicine, University of Ankara, Turkey.
Ugur
M
M
Yazar
O
O
Türker
R K
RK
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects; D013268:Stimulation, Chemical
D015220:Calcium Channels; D006633:Histamine Antagonists; D015222:Sodium Channels; C025170:15(S)-15-methylprostaglandin E1; D006632:Histamine; D012964:Sodium; D000527:Alprostadil; D009638:Norepinephrine