Prostacyclin enhances the evoked-release of substance P and calcitonin gene-related peptide from rat sensory neurons.
Prostacyclin (PGI2) is a potent prostanoid producing various symptoms of inflammation, including an increased sensitivity to noxious stimulation. One component of these PGI2-mediated actions may involve activation or sensitization of sensory neurons to enhance release of neuroactive peptides. We, therefore, examined whether PGI2 and carba prostacyclin (CPGI2), a stable analog of PGI2, could alter the resting and evoked release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) from embryonic rat sensory neurons grown in culture. Treating isolated sensory neurons with CPGI2 (10-1000 nM) for 30 min caused a 3-fold increase in the resting release of both peptides. One nM CPGI2, a concentration that did not alter the resting release, significantly enhanced neuropeptide release evoked by capsaicin, 100 nM bradykinin, or 40 mM KCl. Similarly, 10 nM PGI2 did not alter resting release, but augmented capsaicin-stimulated release of SP and CGRP 2-3 fold. In contrast, prostaglandin F2 alpha was ineffective in altering either resting or capsaicin-evoked peptide release. Our results demonstrate that low concentrations of PGI2 sensitize sensory neurons to other stimuli, whereas higher concentrations evoke release directly. This PGI2-induced augmentation of neuropeptide release may be one mechanism contributing to neurogenic inflammation.
Hingtgen
C M
CM
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46202-5120.
Vasko
M R
MR
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D004357:Drug Synergism; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013373:Substance P / Q000378:metabolism*
D013373:Substance P; C026678:carboprostacyclin; D015237:Dinoprost; D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D001920:Bradykinin