Modulation of CGRP and PGE2 release from isolated rat skin by alpha-adrenoceptors and kappa-opioid-receptors.

Abstract

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.