Modulation of phorbol ester-induced contraction by endogenously released cyclooxygenase products in rat aorta

S. P. Williams, A. K. Campbell, N. Roszell, L. Myatt, G. D. Leikauf, R. M. Rapoport

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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, PGF(2α), and arachidonic acid, but not TxA2. The amount of PGI2 released was greater than that of PGE2 and PGF(2α). Indomethacin blocked the PMA-induced release of PG, but not of arachidonic acid. In PMA-contracted tissues, PGF(2α), 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 PGF(2α)- 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.

Original languageEnglish (US)
Pages (from-to)H1654-H1662
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number5 36-5
DOIs
StatePublished - 1994

Keywords

  • prostaglandin receptor
  • protein kinase C
  • smooth muscle
  • thromboxane receptor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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