TGF-beta3 inhibits pentagastrin-stimulated gastric acid secretion in rats.
BACKGROUND
Transforming growth factor beta3 (TGF-beta3) has been shown to accelerate gastric ulcer healing in rats. However, little is known about the mechanism. In this study we investigated the influence of TGF-beta3 on gastric acid secretion, since gastric hyperacidity is a major cause of gastroduodenal ulcer disease.


METHODS
Male Sprague Dawley rats were equipped with gastric Thomas cannulas and jugular vein catheters. The acute effect of either intravenous TGF-beta3 (400 and 1200 pg/kg/h) or saline (0.15 M) on pentagastrin-stimulated (10 pg/kg/h) gastric acid secretion was evaluated by gastric acid back-titration after 5 days of recovery. Additionally, pentagastrin-stimulated gastric acid secretion was assessed after 48 hours following TGF-beta3 (1200 microg/kg/h) or saline treatment.


RESULTS
Pentagastrin significantly increased gastric acid production. TGF-beta3 significantly reduced pentagastrin-stimulated gastric acid secretion in a dose-dependent manner as early as 15 minutes after application (saline: 124.9+/-14.9 microEq H+/15 min, TGF-beta3: 97.7+/-13.1 9 microEq H+/15 min, p<0.002). Additionally, pretreatment with TGF-beta3 abolished the effect of pentagastrin on gastric acid production. This effect lasted throughout the entire recording period of 48 hours. However, baseline physiological gastric acid production was not altered by TGF-beta3.


CONCLUSIONS
TGF-beta3 inhibits gastric acid secretion when given prior to as well as after pentagastrin treatment. This implicates both a preventive and a therapeutic role of TGF-beta3 in gastroduodenal ulcer disease.
Beckert
Stefan
S
Department of General Surgery, University of Tübingen, Germany.
Wolf
Sebastian C
SC
Farrahi
Farshid
F
Zittel
Tilman T
TT
Coerper
Stephan
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000601:surgery; D006801:Humans; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D008297:Male; D010418:Pentagastrin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3; D014945:Wound Healing / Q000187:drug effects
D011994:Recombinant Proteins; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D010418:Pentagastrin