ISSN:
1437-160X
Keywords:
Substance P
;
Synovial cells
;
Oxyradical production
;
Intracellular Ca2+
;
PKC
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract We examined the intracellular mechanisms of substance P induced oxyradical production in rheumatoid synovial cells by the luminol-dependent chemiluminescence method. After stimulation with substance P (30 μM), single synovial A (macrophage-like) or B (fibroblast-like) cells released oxyradicals such as superoxide anions (OZ) and/or hypochlorous anions (OCl−) under a microscope equipped with an ultrasensitive photonic image intensifier. The substance P induced oxyradical production was blocked by a tachykinin NK1 (NK1) receptor antagonist, GR82334, GTP-binding protein (G-protein) inactivators, GDPβS and islet-activating protein (IAP), and a phospholipase C (PLC) inhibitor, U-73122. Substance P (30 μM) also induced a transient increase in the intracellular Ca2+ concentration ([Ca2+]i) in both synovial A and B cells as measured by a Ca2+ indicator, fura 2. BAPTA-AM and an inositol-1,4-5-triphosphate (IP3) receptor antagonist, heparin, inhibited the substance P induced increase in [Ca2+]i, but they had no effects on oxyradical production. In contrast to the effects of BAPTA-AM and heparin, protein kinase C (PKC) inhibitors, H-7 and calphostin C, completely inhibited substance P induced oxyradical production without any significant effects on [Ca2+]i increase. These findings suggest that the NK1 receptor/PLC-linked diacylglycerol (DAG) formation with the resulting activation of PKC is the main signal transduction pathway for substance P stimulated oxyradical production in synovial cells.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01419729
