Inhibitory effects of calcitonin gene-related peptide on substance-P-induced superoxide production in human neutrophils

European Journal of Pharmacology
T TanabeC Inagaki

Abstract

We examined the mechanisms of the inhibitory effects of calcitonin gene-related peptide (CGRP) on substance-P-induced superoxide anion (O2-) production in human neutrophils. Substance P (30 microM) caused O2- production associated with an inositol-1,4,5-trisphosphate (IP3)-induced transient increase in intracellular Ca2+ concentrations ([Ca2+]i). CGRP (10 microM) significantly inhibited substance-P-induced O2- production and transient increase in [Ca2+]i, but it only slightly suppressed IP3 formation. In addition, CGRP inhibited IP3-induced O2- production and transient increase in [Ca2+]i, caused by exogenous addition of IP3 in saponin-permeabilized neutrophils. These findings suggest that CGRP inhibits the response of neutrophils to substance P through the inhibition of IP3-induced Ca2+ release from intracellular Ca2+ stores. The inhibitory effects of CGRP on substance P- or IP3-induced O2- production and increases in [Ca2+]i were abolished by pretreating the neutrophils with a CGRP receptor antagonist, CGRP-(8 - 37), or cyclic AMP (cAMP)-dependent protein kinase inhibitors, N-[2-(methylamino) ethyl]-5-isoquinoline-sulfonamide dihydrochloride (H-8) and 9-n-hexyl ester derivative of K-572a (8R, 9S, 11 S)-(--)-9-hydroxy-9-methox...Continue Reading

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Citations

Dec 25, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Petra HartmannAndrea Szabó
Jun 20, 2015·Nature Reviews. Neuroscience·Stephen B McMahonDavid L H Bennett
Jul 23, 2004·Physiological Reviews·Susan D Brain, Andrew D Grant
Aug 22, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Youping WangDonna H Wang
Apr 16, 2004·Journal of Endodontics·Javier Caviedes-BucheliJohn Mario González-Escobar
Jul 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Junru WangMartin Hauer-Jensen

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