Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1

J. M. Bathon, D. C. Manning, D. W. Goldman, M. C. Towns, D. Proud

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of its potent proinflammatory properties. We have previously shown bradykinin to be a potent stimulus for the release of prostanoids from interleukin-1 (IL-1)-treated, but not untreated, human synovial cells. We hypothesize that one mechanism by which IL-1 induces responsiveness to bradykinin is by upregulation of number or affinity of kinin receptors on human synovial cells. We performed [3H]bradykinin binding studies in intact human synovial tissue and in cultured human synovial cells. Specific, saturable [3H]bradykinin binding sites in intact synovia were identified by autoradiographic localization and were present in much higher density in rheumatoid, than in osteoarthritis, synovia. In untreated human synovial cells in culture, a single (B2) class of kinin binding sites with a K(d) of 2.3 nM and B(max) of 58 ± 9 fmol/106 cells was demonstrated. In matched experiments, IL-1 treatment enhanced specific [3H]bradykinin binding 1.5- to 2.0-fold above that observed in untreated cells. This enhancement was attributable to an increase in B(max) (53 ± 4 vs. 105 ± 24 fmol/106 cells in untreated and IL-1-treated cells, respectively), rather than an alteration in K(d) (1.7 and 1.4 nM, respectively). The potencies of a series of kinin analogs and antagonists and unrelated peptides in displacing [3H]bradykinin from IL-1-treated cells correlated well with their abilities to induce prostanoid release. These studies provide novel information regarding the nature of kinin receptors in intact human synovia and in cultured human synovial cells, their regulation by IL-1 and their role in IL-1-treated cells in kinin-mediated prostaglandin E2 production.

Original languageEnglish (US)
Pages (from-to)384-392
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - 1992

ASJC Scopus subject areas

  • Pharmacology


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