Sensory neuropeptide interactions in the production of plasma extravasation in the rat.
We used an experimental model of neurogenic inflammation to study the contribution of the primary afferent peptides substance P, calcitonin gene-related peptide, galanin and somatostatin to plasma extravasation in rat synovium. Perfusion of the C-fiber excitotoxin, capsaicin (1.6 mM), through the knee joint of the pentobarbital anesthetized rat, increased plasma extravasation transiently (< 30 min). Perfusion of substance P (1 microM) or calcitonin gene-related peptide (100 nM), two primary afferent neuropeptides that are released by acute capsaicin administration, had no significant effect on plasma extravasation. Co-perfusion of these two neuropeptides, however, evoked an increase in plasma extravasation that was greater than that produced by capsaicin remaining above 250% of the baseline level by the end of the perfusion period (55 min). Capsaicin co-perfused with either galanin (100 nM) or somatostatin (1 microM) failed to increase plasma extravasation. Neither galanin nor somatostatin significantly affected increase in plasma extravasation induced by co-perfusion of substance P plus calcitonin gene-related peptide. Therefore, we suggest that galanin and somatostatin inhibit, presynaptically, the release of substance P and calcitonin gene-related peptide from primary afferent terminals. The interactions among these four neuropeptides provide a novel mechanism for the regulation of primary afferent neurogenic inflammation.
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D019004:Galanin; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010455:Peptides / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000502:physiology; D013373:Substance P / Q000502:physiology
D009479:Neuropeptides; D010455:Peptides; D013373:Substance P; D013004:Somatostatin; D019004:Galanin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin