Abstract
Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PG)F(2α) and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol) produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD(2) and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP(1) and EP(3) receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP(1) antagonist). Butaprost (a selective prostanoid EP(2) receptor agonist), misoprostol (a prostanoid EP(2) and EP(3) receptor agonist), 11-deoxy-PGE(1) (a prostanoid EP(2), EP(3) and EP(4) receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP(1) receptors are involved in positive regulation of the beating rate. Prostanoid EP(1) receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate) and prostanoid TP, DP(1) and EP(1) receptors (which positively regulate the spontaneous beating rate).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Animals
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Animals, Newborn
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Blotting, Western
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Cells, Cultured
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Cloprostenol / pharmacology
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Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / pharmacology
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Dinoprostone / analogs & derivatives
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Dinoprostone / pharmacology
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Dose-Response Relationship, Drug
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Epoprostenol / analogs & derivatives
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Epoprostenol / pharmacology
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Hydantoins / pharmacology
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Iloprost / pharmacology
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Latanoprost
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Myocytes, Cardiac / drug effects*
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Myocytes, Cardiac / metabolism
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Myocytes, Cardiac / physiology*
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Prostaglandin D2 / pharmacology
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Prostaglandins F, Synthetic / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Prostaglandin / agonists*
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Receptors, Prostaglandin / antagonists & inhibitors
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Receptors, Prostaglandin / physiology*
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Receptors, Prostaglandin E, EP1 Subtype / agonists
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Receptors, Prostaglandin E, EP1 Subtype / antagonists & inhibitors
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Receptors, Prostaglandin E, EP1 Subtype / physiology
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Receptors, Thromboxane / agonists
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Receptors, Thromboxane / physiology
Substances
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Hydantoins
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Prostaglandins F, Synthetic
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Receptors, Prostaglandin
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Receptors, Prostaglandin E, EP1 Subtype
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Receptors, Thromboxane
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prostaglandin F2alpha receptor
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Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide
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fluprostenol
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beraprost
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Cloprostenol
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sulprostone
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Latanoprost
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BW 245C
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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Epoprostenol
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Iloprost
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Dinoprostone
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Prostaglandin D2
Grants and funding
HM received a grant from the French Society of Pharmacology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.