Inhibitory effect of PACAP-38 on acute neurogenic and non-neurogenic inflammatory processes in the rat.
Inhibitory actions of pituitary adenylate cyclase activating polypeptide (PACAP) have been described on cellular/vascular inflammatory components, but there are few data concerning its role in neurogenic inflammation. In this study we measured PACAP-like immunoreactivity with radioimmunoassay in the rat plasma and showed a two-fold elevation in response to systemic stimulation of capsaicin-sensitive sensory nerves by resiniferatoxin, but not after local excitation of cutaneous afferents. Neurogenic plasma extravasation in the plantar skin induced by intraplantar capsaicin or resiniferatoxin, as well as carrageenan-induced paw edema were significantly diminished by intraperitoneal PACAP-38. In summary, these results demonstrate that PACAP is released from activated capsaicin-sensitive afferents into the systemic circulation. It diminishes acute pure neurogenic and mixed-type inflammatory reactions via inhibiting pro-inflammatory mediator release and/or by acting at post-junctional targets on the vascular endothelium.
Helyes
Z
Z
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Hungary.
Pozsgai
G
G
Börzsei
R
R
Németh
J
J
Bagoly
T
T
Márk
L
L
Pintér
E
E
Tóth
G
G
Elekes
K
K
Szolcsányi
J
J
Reglodi
D
D
D000208:Acute Disease; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity; D002351:Carrageenan / Q000008:administration & dosage / Q000633:toxicity; D004224:Diterpenes / Q000008:administration & dosage / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007249:Inflammation / Q000097:blood* / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D008297:Male; D013058:Mass Spectrometry; D020078:Neurogenic Inflammation / Q000097:blood* / Q000139:chemically induced; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
D004224:Diterpenes; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002351:Carrageenan; C024353:resiniferatoxin; D002211:Capsaicin