Modulation of CGRP and PGE(2) release from isolated rat skin by alpha-adrenoceptors and kappa-opioid-receptors

Norepinephrine (NE) reduces the release of neuropeptides from central termi nals of primary afferent neurones by presynaptic inhibition. We investigate d whether NE also affects stimulus-induced intracutaneous calcitonin gene-r elated peptide (CGRP) and secondary prostaglandin E-2 (PGE(2)) release. For comparison. kappa -opioid effects were examined. Antidromic electrical ner ve stimulation resulted in significant increases in the release of CGRP and PGE(2). The PGE(2) release was prevented by selective activation of alpha (2)-adrenoceptors whereas the CGRP release was not changed. In contrast, se lective kappa -opioid receptor activation diminished electrically evoked re lease of both CGRP and PGE-(2). We conclude that NE affected stimulated PGE (2) release via alpha (2)-adrenoceptors on cells other than cutaneous affer ents while kappa -opioid receptors are expressed in peripheral terminals of cutaneous afferents and their activation reduced CGRP release and secondar y PGE(2) formation. NeuroReport 12:2097-2100 (C) 2001 Lippincott Williams & Wilkins.