LOCALIZATION AND CHARACTERIZATION OF SUBSTANCE-P BINDING TO HUMAN SYNOVIAL TISSUE IN RHEUMATOID-ARTHRITIS

The neuropeptide substance P is found in perivascular and free unmyelinated nerve fibres in human synovial tissue. Quantitative receptor autoradiography was used to show specific, high affinity (K(d) = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (B(max) = 27.8 (7.9) amol/mm2) binding sites for substance P Bolton Hunter-labelled with iodine-125 localised to vascular endothelial cells in human synovial tissue. The binding could be saturated, was reversible, and was dependent on the magnesium concentration. Unlabelled substance P and neurokinin A competitively inhibited specific binding with 50% inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively. Neurokinin B (mu-mol/l) and calcitonin gene related peptide (1-mu-mol/l) did not inhibit binding. These binding sites show characteristics of the neurokinin 1 tachykinin receptor subtype. This provides further evidence that substance P may play a part in the vascular control of human synovium and may influence inflammatory processes in joints.