PROSTACYCLIN ENHANCES THE EVOKED-RELEASE OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE FROM RAT SENSORY NEURONS

Prostacyclin (PGI(2)) is a potent prostanoid producing various symptom s of inflammation, including an increased sensitivity to noxious stimu lation. One component of these PGI(2)-mediated actions may involve act ivation or sensitization of sensory neurons to enhance release of neur oactive peptides. We, therefore, examined whether PGI(2) and carba pro stacyclin (CPGI(2)), a stable analog of PGI(2), could alter the restin g and evoked release of the neuropeptides, substance P (SP) and calcit onin gene-related peptide (CGRP) from embryonic rat sensory neurons gr own in culture. Treating isolated sensory neurons with CPGI(2) (10-100 0 nM) for 30 min caused a 3-fold increase in the resting release of bo th peptides. One nM CPGI(2), a concentration that did not alter the re sting release, significantly enhanced neuropeptide release evoked by c apsaicin, 100 nM bradykinin, or 40 mM KCI. Similarly, 10 nM PGI(2) did not alter resting release, but augmented capsaicin-stimulated release of SP and CORP 2-3 fold. In contrast, prostaglandin F-2 alpha was ine ffective in altering either resting or capsaicin-evoked peptide releas e. Our results demonstrate that low concentrations of PGI(2) sensitize sensory neurons to other stimuli, whereas higher concentrations evoke release directly. This PGI(2)-induced augmentation of neuropeptide re lease may be one mechanism contributing to neurogenic inflammation.