Pönicke K, Giessler C, Grapow M, Heinroth-Hoffmann I, Becker K, Osten B, Brodde O E
Institute of Pharmacology and Toxicology, Martin-Luther-University of Halle-Wittenberg, Magdeburger Str. 4, D-06097 Halle (Saale), Germany.
Br J Pharmacol. 2000 Apr;129(8):1723-31. doi: 10.1038/sj.bjp.0703243.
The aim of this study was to characterize the receptor subtype involved in cardiac effects of prostanoids. For this purpose we determined in neonatal and adult rat cardiomyocytes effects of prostanoids on inositol phosphate (InsP)-formation (assessed as accumulation of total [(3)H]-InsP's in myo-[(3)H]-inositol pre-labelled cells) and on rate of protein synthesis (assessed as [(3)H]-phenylalanine incorporation), and on contractile force in left ventricular strips of the rat heart. For comparison, effects of prostanoids on InsP-formation and contractile force were determined in rat thoracic aorta, a classical TP-receptor containing tissue. Prostanoid increased InsP-formation and rate of protein synthesis in neonatal as well as adult rat cardiomyocytes; the order of potency was in neonatal (PGF(2alpha)>PGD(2)> or =PGE(2)> or =U 46619>PGE(1)) and adult (PGF(2alpha)>PGD(2)> or =PGE(2)>U 46619) rat cardiomyocytes well comparable. Moreover, in electrically driven left ventricular strips PGF(2alpha) caused positive inotropic effects (pD(2) 7.5) whereas U 46619 (up to 1 microM) was uneffective. In contrast, in rat thoracic aorta U 46619 was about 100 times more potent than PGF(2alpha) in increasing InsP-formation and contractile force. The TP-receptor antagonist SQ 29548 only weakly antagonized prostanoid-induced increases in rate of protein synthesis (pK(B) about 6) in rat cardiomyocytes but was very potent (pK(B) about 8-9) in antagonizing prostanoid-induced increases in InsP-formation and contractile force in rat aorta. We conclude that, in cardiomyocytes of neonatal and adult rats, the prostanoid-receptor mediating increases in InsP-formation and rate of protein synthesis is a FP-receptor. Moreover, stimulation of these cardiac FP-receptors can mediate increases in contractile force.
本研究的目的是确定参与前列腺素心脏效应的受体亚型。为此，我们测定了前列腺素对新生大鼠和成年大鼠心肌细胞中肌醇磷酸（InsP）形成（以预先用肌 - [³H] - 肌醇标记的细胞中总[³H] - InsP的积累来评估）、蛋白质合成速率（以[³H] - 苯丙氨酸掺入来评估）以及大鼠心脏左心室条带收缩力的影响。作为比较，我们还测定了前列腺素对大鼠胸主动脉（一种典型的含有TP受体的组织）中InsP形成和收缩力的影响。前列腺素可增加新生大鼠和成年大鼠心肌细胞中的InsP形成和蛋白质合成速率；在新生大鼠心肌细胞（PGF₂α > PGD₂ ≥ PGE₂ ≥ U 46619 > PGE₁）和成年大鼠心肌细胞（PGF₂α > PGD₂ ≥ PGE₂ > U 46619）中，其效力顺序具有很好的可比性。此外，在电驱动的左心室条带中，PGF₂α引起正性肌力作用（pD₂ 7.5），而U 46619（高达1 μM）无效。相比之下，在大鼠胸主动脉中，U 46619在增加InsP形成和收缩力方面的效力比PGF₂α强约100倍。TP受体拮抗剂SQ 29548仅微弱拮抗前列腺素诱导的大鼠心肌细胞蛋白质合成速率增加（pK₇约为6），但在拮抗前列腺素诱导的大鼠主动脉中InsP形成和收缩力增加方面非常有效（pK₇约为8 - 9）。我们得出结论，在新生大鼠和成年大鼠的心肌细胞中，介导InsP形成和蛋白质合成速率增加的前列腺素受体是FP受体。此外，刺激这些心脏FP受体可介导收缩力增加。
