Prostanoid Receptors Involved in Regulation of the Beating Rate of Neonatal Rat Cardiomyocytes

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).

Confirmation of the Cardiac Safety of PGF2αReceptor Antagonist OBE022 in a First‐in‐Human Study in Healthy Subjects, Using Intensive ECG Assessments

“…Some of the concentration-QTcF models for parent OBE002 (models both and OBE022; Table 2) tended to indicate a nonsignificant negative slope. An effect on cardiac function of exposure to the FP antagonists OBE002 or its parent OBE022 could be excluded despite the reported action of FP agonists on cardiac function in vitro 8,9,11,[30][31][32] and reports of blood pressure elevation in response to topical application of FP agonists. 33 This is consistent with previous clinical studies of allosteric FP antagonists that showed no QTc prolongation attributable to drug administration.…”

Whole body periodic acceleration (pGz) preserves heart rate variability after cardiac arrest

“…34 Thus, enhanced eNOS and nNOS as produced by pGz may reinforce and increase vagal tone after cardiac arrest and thus increase HRV in pGz treated animals.pGz has also been shown to induce endothelial production of Prostaglandin E 2 . 35 In isolated ventricular cardiomyocytes, prostaglandin E 2 increases the intrinsic beating rate in a dose dependent manner, 36 however its effect on HRV is unknown and remain to be studied.…”

The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension

“…Prostanoids are a group of lipid-based molecules that modulate vascular tone, platelet function, inflammation, cell proliferation and cardiac function (161). Prostanoids exerts their effects with GPCR prostanoid receptors including DP 1−2 , EP 1−4 , FD, IP, and TP (162) and majority of them are present on cardiomyocytes (163). The prostacyclin receptor (IP) is abundantly expressed in blood vessels, leukocytes, and platelets, and is activated by binding of the prostacyclin and its analogs.…”