Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9001774 | Biochemical Pharmacology | 2005 | 11 Pages |
Abstract
Pre-contraction with the thromboxane-mimetic U46619 enhances the subsequent α2-adrenoceptor-mediated vasoconstriction in the porcine ear artery through an enhanced activation of ERK-MAP kinase. In this study we determined the role of cPLA2 in this enhanced response, and determined whether vasopressin is also able to enhance α2-adrenoceptor-mediated vasoconstriction through the same pathway. The cPLA2 inhibitors AACOCF3 (50 μM) and MAFP (50 μM) both inhibited the U46619-enhanced α2-adrenoceptor response, but had no effect on the direct α2-adrenoceptor response. AACOCF3 also inhibited the enhanced ERK activation associated with the enhanced α2-adrenoceptor-mediated vasoconstriction. Pre-contraction with arachidonic acid mimicked the effect of U46619 by enhancing the contractile response to the α2-adrenoceptor agonist UK14304 (1 μM) and enhancing the α2-adrenoceptor-mediated ERK activation. Pre-contraction with vasopressin also enhanced the contractile response to UK14304, but neither PD98059 (50 μM) nor AACOCF3 (50 μM) had any effect this vasopressin-enhanced response, indicating that neither the ERK pathway, nor cPLA2 are involved in vasopressin-enhanced responses. The α2-adrenceptor-stimulated activation of ERK was also unaffected by pre-contraction with vasopressin. On the other hand, inhibition of PKCζ inhibited the enhanced α2-adrenoceptor contraction after pre-contraction with both U46619 and vasopressin. This study demonstrates that α2-adrenoceptor-mediated vasoconstriction can be enhanced through two different pathways-one dependent upon the enhanced activation of ERK-MAP kinase through activation of cPLA2, and the other through a different, ERK/cPLA2-independent pathway.
Keywords
HELSSERKE-64TBS-TPKCAEBSFPLA2Tris-buffered saline containing 0.1% Tween-20phospholipase A2Adrenergic agonistsContractile functionanalysis of the varianceANOVAMEKProtein kinase Cmitogen-activated protein kinasemitogen-activated protein kinase kinaseSecond messengersMAP kinaseextracellular signal-regulated kinasePorcine
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Authors
B. Bhattacharya, R. Williams, M.L. Latif, R.E. Roberts,