Modulation of CGRP and PGE2 release from isolated rat skin by alpha-adrenoceptors and kappa-opioid-receptors.
Norepinephrine (NE) reduces the release of neuropeptides from central terminals of primary afferent neurones by presynaptic inhibition. We investigated whether NE also affects stimulus-induced intracutaneous calcitonin gene-related peptide (CGRP) and secondary prostaglandin E2 (PGE2) release. For comparison, kappa-opioid effects were examined. Antidromic electrical nerve stimulation resulted in significant increases in the release of CGRP and PGE2. The PGE2 release was prevented by selective activation of alpha2-adrenoceptors whereas the CGRP release was not changed. In contrast, selective kappa-opioid receptor activation diminished electrically evoked release of both CGRP and PGE2. We conclude that NE affected stimulated PGE2 release via alpha2-adrenoceptors on cells other than cutaneous afferents while kappa-opioid receptors are expressed in peripheral terminals of cutaneous afferents and their activation reduced CGRP release and secondary PGE2 formation.
Averbeck
B
B
Department of Physiology and Experimental Pathophysiology, University of Erlangen-Nürnberg, Universitätsstr. 17, D-91054 Erlangen, Germany.
Reeh
P W
PW
Michaelis
M
M
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D008024:Ligands; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists; D008024:Ligands; D009292:Narcotic Antagonists; D009294:Narcotics; D018341:Receptors, Adrenergic, alpha-2; D017473:Receptors, Opioid, kappa; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D009638:Norepinephrine