Williams S P, Campbell A K, Roszell N, Myatt L, Leikauf G D, Rapoport R M
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio.
Am J Physiol. 1994 Nov;267(5 Pt 2):H1654-62. doi: 10.1152/ajpheart.1994.267.5.H1654.
This study tests the hypothesis that prostaglandins (PGs) released in response to phorbol esters act as modulators of the phorbol ester-induced smooth muscle contraction. The rate and magnitude of the phorbol 12-myristate 13-acetate (PMA)-induced contraction of deendothelialized rat aorta were decreased by the cyclooxygenase inhibitor, indomethacin. The thromboxane (Tx) A2/PGH2 receptor antagonist, SQ-29548, also inhibited PMA-induced contraction, and the magnitude of inhibition was greater than that due to indomethacin. PMA induced the release of PGI2, PGE2, PGF2 alpha, and arachidonic acid, but not TxA2. The amount of PGI2 released was greater than that of PGE2 and PGF2 alpha. Indomethacin blocked the PMA-induced release of PG, but not of arachidonic acid. In PMA-contracted tissues, PGF2 alpha, PGE2, and the stable PGI2 and PGH2 analogues, carbacyclin and U-46619, respectively, induced further contraction. Pretreatment of PMA-contracted tissues with SQ-29548 partially inhibited the PGF2 alpha- and PGE2-induced contractions, completely inhibited contraction to U-46619, and reversed the carbacyclin-induced contraction to relaxation. These results demonstrate that, in rat aorta, PMA induces the release of PGs that exert both contractile and relaxant effects but whose net effect is to accelerate and augment the contraction induced by PMA. The PG-induced increase in PMA contraction is mediated, in large part, through TxA2/PGH2 receptor activation. The ability of various PGs, including carbacyclin, to activate the TxA2/PGH2 receptor suggests that one or more of these PGs, in addition to, presumably, PGH2, may be responsible for the increase in PMA contraction. PGI2 is the only endogenously released PG that can account for the relaxant effect.
响应佛波酯释放的前列腺素（PGs）作为佛波酯诱导的平滑肌收缩的调节剂。环氧化酶抑制剂吲哚美辛降低了去内皮大鼠主动脉对佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）诱导的收缩速率和幅度。血栓素（Tx）A2/PGH2受体拮抗剂SQ - 29548也抑制PMA诱导的收缩，且抑制幅度大于吲哚美辛所致的抑制幅度。PMA诱导了前列环素（PGI2）、前列腺素E2（PGE2）、前列腺素F2α（PGF2α）和花生四烯酸的释放，但未诱导血栓素A2（TxA2）的释放。PGI2的释放量大于PGE2和PGF2α的释放量。吲哚美辛阻断了PMA诱导的PG释放，但未阻断花生四烯酸的释放。在PMA收缩的组织中，PGF2α、PGE2以及稳定的PGI2和PGH2类似物卡前列环素和U - 46619分别诱导了进一步的收缩。用SQ - 29548对PMA收缩的组织进行预处理，部分抑制了PGF2α和PGE2诱导的收缩，完全抑制了对U - 46619的收缩，并使卡前列环素诱导的收缩转变为舒张。这些结果表明，在大鼠主动脉中，PMA诱导PGs的释放，这些PGs发挥收缩和舒张作用，但其净效应是加速和增强PMA诱导的收缩。PG诱导的PMA收缩增加在很大程度上是通过TxA2/PGH2受体激活介导的。包括卡前列环素在内的各种PG激活TxA2/PGH2受体的能力表明，除了推测的PGH2外，这些PG中的一种或多种可能是PMA收缩增加的原因。PGI2是唯一能解释舒张作用的内源性释放的PG。
