Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats.
TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg, intraperitoneally) TLQP-21 administration on gastric acid secretion in pylorus-ligated rats. The mechanisms involved in such activity were also examined. Central TLQP-21 injection significantly reduced gastric acid volume and dose-dependently inhibited total acid output (ED(50) = 2.71 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 antisecretory activity was prevented by cysteamine (300 mg/kg, subcutaneously), a depletor of somatostatin, by indomethacin (0.25 mg/rat, intracerebroventricularly), a non-selective cyclooxygenase inhibitor, and by functional ablation of sensory nerves by capsaicin. We conclude that TLQP-21 could be considered a new member of the large group of regulatory peptides affecting gastric acid secretion. The central inhibitory effect of TLQP-21 on gastric acid secretion is mediated by endogenous somatostatin and prostaglandins and requires the integrity of sensory nerve fibres.
Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Via Vanvitelli, 32, 20129, Milan, Italy. valeria.sibilia@unimi.it
Valeria
V
Sibilia
Francesca
F
Pagani
Ilaria
I
Bulgarelli
Giovanni
G
Tulipano
Roberta
R
Possenti
Francesca
F
Guidobono
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects*
D009479:Neuropeptides; D010446:Peptide Fragments; C522412:TLQP-21 peptide; C522413:VGF peptide