Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins.
The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.
Vongthavaravat
Verapan
V
Department of Medicine, University of Oklahoma Health Sciences Center, and Oklahoma City Department of Veterans Affairs, Medical Center, Oklahoma City, Oklahoma, USA.
Mesiya
Sikandar
S
Saymeh
Layth
L
Xia
Yang
Y
Harty
Richard F
RF
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D002211:Capsaicin / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D005756:Gastritis / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D009475:Neurons, Afferent; D009479:Neuropeptides / Q000032:analysis; D011336:Probability; D011453:Prostaglandins / Q000032:analysis; D011877:Radionuclide Imaging; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D013270:Stomach / Q000000981:diagnostic imaging / Q000187:drug effects; D013373:Substance P / Q000032:analysis*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D009479:Neuropeptides; D011453:Prostaglandins; D016211:Transforming Growth Factor alpha; D013373:Substance P; D000431:Ethanol; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin