Bradykinin is a potent and relatively selective stimulus for cytosolic calcium elevation in human synovial cells

Joan M. Bathon, John C. Croghan, Donald W. MacGlashan, David Proud

Research output: Contribution to journalArticle

Abstract

Previously, we have shown that bradykinin elicits the production of prostaglandin E2 (PGE2) in human synovial cells only after pre-exposure of the cells to IL-1. The observation that calcium ionophores, but not a variety of physiologic receptor-mediated agonists, can mimic bradykinin in its synergy with IL-1 led us to hypothesize that the ability of bradykinin to induce prostanoid synthesis was a result of its selective ability (among physiologic agonists) to raise the cytosolic free ionized calcium concentration ([Ca2+](i)) levels of synovial cells. Extending this hypothesis, it follows that the relative potency of an agonist in inducing PGE2 production from IL-1-treated cells should be dependent on its ability to raise [Ca2+](i). In these studies, we have confirmed the potent ability of bradykinin to elevate [Ca2+](i) in resting human synovial cells. That the effect of bradykinin on [Ca2+](i) was mediated through the previously described synovial cell kinin receptor was confirmed by a pharmacologic profile consistent with a high affinity B2 kinin receptor. Furthermore, the relative specificity and potency of the PGE2 response of bradykinin in IL- 1-treated cells was paralleled, in resting cells, by a similar pattern in the [Ca2+](i) response. Finally, IL-1 had no direct effect on [Ca2+](i) levels, nor did it alter agonist-induced elevations in [Ca2+](i). We conclude that the potency of a receptor-mediated agonist in inducing prostanoid synthesis in synovial cells is dependent on its ability to raise [Ca2+](i). However, this effect is not enough, in and of itself, to induce prostanoid synthesis, the concomitant induction by IL-1 of a PG-generating enzyme is also required.

Original languageEnglish (US)
Pages (from-to)2600-2608
Number of pages9
JournalJournal of Immunology
Volume153
Issue number6
StatePublished - Sep 15 1994

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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