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Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1.
J Pharmacol Exp Ther. 1992 Jan; 260(1):384-92.JP

Abstract

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 Kd of 2.3 nM and Bmax of 58 +/- 9 fmol/10(6) 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 Bmax (53 +/- 4 vs. 105 +/- 24 fmol/10(6) cells in untreated and IL-1-treated cells, respectively), rather than an alteration in Kd (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.

Authors+Show Affiliations

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1309881

Citation

Bathon, J M., et al. "Characterization of Kinin Receptors On Human Synovial Cells and Upregulation of Receptor Number By Interleukin-1." The Journal of Pharmacology and Experimental Therapeutics, vol. 260, no. 1, 1992, pp. 384-92.
Bathon JM, Manning DC, Goldman DW, et al. Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1. J Pharmacol Exp Ther. 1992;260(1):384-92.
Bathon, J. M., Manning, D. C., Goldman, D. W., Towns, M. C., & Proud, D. (1992). Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1. The Journal of Pharmacology and Experimental Therapeutics, 260(1), 384-92.
Bathon JM, et al. Characterization of Kinin Receptors On Human Synovial Cells and Upregulation of Receptor Number By Interleukin-1. J Pharmacol Exp Ther. 1992;260(1):384-92. PubMed PMID: 1309881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of kinin receptors on human synovial cells and upregulation of receptor number by interleukin-1. AU - Bathon,J M, AU - Manning,D C, AU - Goldman,D W, AU - Towns,M C, AU - Proud,D, PY - 1992/1/1/pubmed PY - 1992/1/1/medline PY - 1992/1/1/entrez SP - 384 EP - 92 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 260 IS - 1 N2 - 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 Kd of 2.3 nM and Bmax of 58 +/- 9 fmol/10(6) 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 Bmax (53 +/- 4 vs. 105 +/- 24 fmol/10(6) cells in untreated and IL-1-treated cells, respectively), rather than an alteration in Kd (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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1309881/Characterization_of_kinin_receptors_on_human_synovial_cells_and_upregulation_of_receptor_number_by_interleukin_1_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1309881 DB - PRIME DP - Unbound Medicine ER -