Role of eicosanoids in vasopressin-induced calcium mobilization in A7r5 vascular smooth muscle cells

M. Thibonnier, A. L. Bayer, C. L. Laethem, D. R. Koop, M. S. Simonson

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The role of arachidonic acid (AA) and its metabolites in vasopressin (AVP)-induced calcium mobilization in A7r5 aortic smooth muscle cells was explored by intracellular calcium monitoring, [14C]AA labeling, and high- performance liquid chromatography (HPLC) techniques. In fura 2-loaded A7r5 cells, AA potentiated AVP-stimulated increase in intracellular free Ca2+ ([Ca2+](i)). The cyclooxygenase inhibitor indomethacin reduced both the AA- and AVP-induced influx of extracellular Ca2+. AVP-induced [Ca2+](i) transients were not altered by lipoxygenase inhibitors but were reduced in a dose-dependent fashion by ketoconazole, an inhibitor of cytochrome P-450 monooxygenases. Among several epoxygenase metabolites of AA tested, 5,6- epoxyeicosatrienoic acid potentiated AVP-induced [Ca2+](i) transients. Reverse-phase HPLC analysis of lipid extracts from A7r5 cells prelabeled with [14C]AA isolated a radioactive peak that did not coelute with established products of cyclooxygenase-, lipoxygenase-, or cytochrome P-450-catalyzed oxidations of AA. This peak was significantly increased after AVP stimulation and was completely blocked by preincubation with ketoconazole. Thus the stimulation of V1-vascular AVP receptors of A7r5 cells triggers several cytoplasmic signaling pathways involving AA metabolite formation through the cyclooxygenase and epoxygenase pathways.

Original languageEnglish (US)
Pages (from-to)E108-E114
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume265
Issue number1 28-1
StatePublished - Jan 1 1993

Keywords

  • arachidonic acid metabolites
  • calcium fluxes
  • vasopressin receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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