Modulation of CGRP and PGE2 release from isolated rat skin by α-adrenoceptors and κ-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 E-2 (PGE(2)) release. For comparison. kappa -opioid effects were examined. Antidromic electrical nerve 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, selective kappa -opioid receptor activation diminished electrically evoked release of both CGRP and PGE-(2). We conclude that NE affected stimulated PGE(2) release via alpha (2)-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 PGE(2) formation. NeuroReport 12:2097-2100 (C) 2001 Lippincott Williams & Wilkins.