title: Bradykinin is a potent and relatively selective stimulus for cytosolic calcium elevation in human synovial cells.
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.
authors.affiliation: Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD 21224.
authors.forename: J M
authors.initials: JM
authors.lastname: Bathon
authors.forename: J C
authors.initials: JC
authors.lastname: Croghan
authors.forename: D W
authors.initials: DW
authors.lastname: MacGlashan
authors.forename: D
authors.initials: D
authors.lastname: Proud
mesh_terms: D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D011458:Prostaglandins E; D001920:Bradykinin; D002118:Calcium