Role of bradykinin in inflammatory arthritis: identification and functional analysis of bradykinin receptors on human synovial fibroblasts.
Receptor type and function of bradykinin (BK) receptors on human synovial fibroblasts (HSF) was determined. Scatchard analysis of [3H]BK saturation binding to intact synovial cells revealed a single binding site, with a Kd of 3.8 +/- 0.6 nM. HSF express approximately 50,000 BK sites/cell. Specificity of [3H]BK binding was confirmed by the ability of several BK peptide agonists and antagonists to inhibit binding in a dose dependent manner. The rank order of potency for agonist inhibition of [3H]BK and the inability of selective antagonists of the B1-type to displace binding suggest that the BK receptor on HSF is a B2 subtype receptor. The addition of BK to HSF caused a time and concentration dependent increase in PGE2 production. This BK induced PGE2 production was blocked by specific B2 type BK antagonists and not by B1 antagonists. The results of this study identify B2 type BK receptors on synovial fibroblasts and suggest that BK may be a primary mediator in inflammatory arthritis.
Uhl
J
J
Department of Inflammation, Sterling Research Group, Rensselaer, NY 12144.
Singh
S
S
Brophy
L
L
Faunce
D
D
Sawutz
D G
DG
D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D015232:Dinoprostone; D001920:Bradykinin