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)F2α 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 (PGD2 and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP1 and EP3 receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP1 antagonist). Butaprost (a selective prostanoid EP2 receptor agonist), misoprostol (a prostanoid EP2 and EP3 receptor agonist), 11-deoxy-PGE1 (a prostanoid EP2, EP3 and EP4 receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP1 receptors are involved in positive regulation of the beating rate. Prostanoid EP1 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, DP1 and EP1 receptors (which positively regulate the spontaneous beating rate).
Highlights
IntroductionThe prostanoid receptors include the DP, EP, FP, IP1 and TP receptors [2,3], which preferentially bind prostaglandin D (PGD), PGE, PGF, PGI and thromboxane A (TXA), respectively, and belong to the G-protein-coupled receptor superfamily [4]
Prostanoids exert a wide variety of effects on cardiac tissue [1]
The main objective of the present study was to identify the prostanoid receptors involved in regulation of the spontaneous beating rate of neonatal rat cardiomyocytes
Summary
The prostanoid receptors include the DP, EP, FP, IP1 and TP receptors [2,3], which preferentially bind prostaglandin D (PGD), PGE, PGF, PGI and thromboxane A (TXA), respectively, and belong to the G-protein-coupled receptor superfamily [4]. Endogenous prostanoids tend to bind most strongly to a given prostanoid receptor class, there is a marked degree of crossreactivity between these ligands and the entire receptor family [2,5] This taxonomy has only been described fairly recently, following the availability of selective agonists and, to lesser degree, a few selective antagonists [6]. Molecular biology techniques have confirmed this pharmacological classification via the cloning of cDNAs for representatives of each type of prostanoid receptor in a number of species
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