TLQP-21, a VGF-derived peptide, prevents ethanol-induced gastric lesions: insights into its mode of action.
OBJECTIVE
TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown.


METHODS
We investigated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat. The mechanisms involved in such activity were also examined.


RESULTS
Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric lesions (ED(50) = 3.16 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied by a significant increase in gastric prostaglandin E(2) (PGE(2)) production linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP-21 gastroprotection.


CONCLUSIONS
This study shows for the first time that central TLQP-21 exerts a protective action on the gastric mucosa exposed to the noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived NO and PGE(2), and requires the integrity of sensory nerve fibers.
Sibilia
Valeria
V
Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Milano, Italy. valeria.sibilia@unimi.it
Pagani
Francesca
F
Bulgarelli
Ilaria
I
Mrak
Emanuela
E
Broccardo
Maria
M
Improta
Giovanna
G
Severini
Cinzia
C
Possenti
Roberta
R
Guidobono
Francesca
F
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D012333:RNA, Messenger; C522412:TLQP-21 peptide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin