Localisation and characterisation 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 (Kd = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (Bmax = 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 (mumol/l) and calcitonin gene related peptide (1 mumol/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.
Walsh
D A
DA
Inflammation Group, London Hospital, Whitechapel, United Kingdom.
Mapp
P I
PI
Wharton
J
J
Rutherford
R A
RA
Kidd
B L
BL
Revell
P A
PA
Blake
D R
DR
Polak
J M
JM
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001345:Autoradiography; D001808:Blood Vessels / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D013373:Substance P / Q000378:metabolism*; D013583:Synovial Membrane / Q000098:blood supply / Q000378:metabolism*
D007457:Iodine Radioisotopes; D013373:Substance P