Denervation and NKI receptor block modulate stimulated CGRP and PGE2 release from rat skin.
We investigated the possible neurogenic origin of prostaglandin E2 (PGE2) in the rat skin, in vitro. The hairy skin of one hindpaw was denervated and one week later the dorsal hindpaws were skinned to study the release of calcitonin gene-related peptide (CGRP) and PGE2 using the EIA technique. Stimulation with bradykinin (BK) caused a significant release of CGRP (1.4-fold increase) and PGE2 (3-fold) which was massively augmented under neurokinin I (NKI) receptor antagonist treatment (CGRP: 4-fold, PGE2: 5-fold). In denervated skin the BK-evoked CGRP release was lost whereas the PGE2 release was unchanged. Thus, neither nerve endings nor neuropeptides contribute essentially to BK-induced PGE2 release in the skin. However, excessive neuropeptide levels, as under NKI blockade facilitate PGE2 formation, which may play a role in sustained inflammation.
Sauer
S K
SK
University of Erlangen, Department of Physiology and Experimental Pathophysiology, Germany.
Averbeck
B
B
Reeh
P W
PW
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003714:Denervation; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006614:Hindlimb; D066298:In Vitro Techniques; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012867:Skin / Q000294:innervation* / Q000378:metabolism*
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; C085215:SR 140333; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin