Calcitonin gene-related peptide and prostaglandin E2 but not substance P release induced by antidromic nerve stimulation from rat skin in vitro.
The liberation of calcitonin gene-related peptide from rat skin in vitro induced by antidromic electrical stimulation of unmyelinated units is demonstrated. Prostaglandin E2 was released concomitantly during C-fiber stimulation. A dose-dependent increase in prostaglandin E2 content of the eluate was also observed in response to stimulation with substance P (10(-7) to 10(-5) M) and calcitonin gene-related peptide (10(-6) and 10(-5) M). In contrast, prostaglandin E2 did not induce measurable release of neuropeptides. The amount of calcitonin gene-related peptide released during suprathreshold electrical stimulation increased with pulse frequency. Calcitonin gene-related peptide and prostaglandin release were completely inhibited in the presence of EMD 61753, a selective kappa-opioid receptor agonist. No significant release of substance P was observed. The data demonstrate a primary release of calcitonin gene-related peptide from unmyelinated but not myelinated primary afferents in the rat skin, which is accompanied by a secondary liberation of prostaglandin E2, connecting neurogenic inflammation to general mechanisms of inflammation.
Institute of Physiology and Experimental Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
M
M
Kress
C
C
Guthmann
B
B
Averbeck
P W
PW
Reeh
D000081:Acetamides / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009412:Nerve Fibers / Q000737:chemistry / Q000378:metabolism*; D020078:Neurogenic Inflammation / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000502:physiology; D012867:Skin / Q000294:innervation*; D013268:Stimulation, Chemical; D013373:Substance P / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
D000081:Acetamides; D000701:Analgesics, Opioid; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D013373:Substance P; C092095:asimadoline; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone