抄録
Calcitonin gene-related peptide (CGRP) is known to be co-localized with substance P (SP) in sensory C-fibers. We investigated the interaction between these neuropeptides in the superoxide (O-2) production of human neutrophils. SP and SP4-11 fragment (10-100μM) induced O-2 production of neutrophils in a dose dependent manner. Phospholipase C inhibitor, U-73122 and neomycin, suppressed the O-2 production by SP and SP4-11 fragment. CGRP (10-20μM) reduced the SF induced O-2 production, and this effect of CGRP was blocked by CGRP receptor antagonist, CGRP8-37 (10μM) . Dibutyryl-cyclic AMP (dBcAMP; 0.5 mM) and phosphodi-esterase inhibitors, 3-isobutyl-1-methyl xanthine (IBMX, 5μM) and theophylline (0.5 mM), also inhibited SP-induced O-2 production. The cAMP-dependent protein kinase (A-kinase) inhibitors, H-8 (10μM) and KT5720 (50 nM), suppressed the CGRP-induced effect. These data suggest that CGRP inhibits the SF induced O-2 production in neutrophils by interfering with phosphoinositide signaling through receptor linked activation of the cAMP/A-kinase-dependent pathway.
