Inflammatory mediators release calcitonin gene-related peptide from dorsal root ganglion neurons of the rat

Abstract

The interactions between the inflammatory mediators bradykinin, serotonin, prostaglandin E 2 and acid pH were studied in rat dorsal root ganglion neurons in culture. For this purpose, the cultures were stimulated by inflammatory mediators (bradykinin, serotonin, prostaglandin E 2, 10 −5 M each) or acid solution (pH 6.1) for 5 min and the content of calcitonin gene-related peptide was determined in the supernatant before, during and after stimulation, using an enzyme immunoassay. Acid solution resulted in a threefold increase of the basal calcitonin gene-related peptide release which was entirely dependent on the presence of extracellular calcium. The release could not be blocked by the addition of the capsaicin antagonist capsazepine (10 −5 M). Bradykinin (10 −5 M) caused a 50% increase of the basal calcitonin gene-related peptide release which was again dependent on the presence of extracellular calcium, whereas serotonin and prostaglandin E 2 were each ineffective at 10 −5 M concentration. The combination of bradykinin, serotonin and prostaglandin E 2 led to a fivefold increase of the calcitonin gene-related peptide release which could not be further enhanced by acidification. The competitive capsaicin receptor antagonist capsazepine (10 −5 M) significantly reduced the release induced by the combination of bradykinin, serotonin and prostaglandin E 2. It is suggested that the inflammatory mediators co-operate and together may act as endogenous agonists at the capsaicin receptor to cause calcium influx and consecutive neuropeptide release.