Transforming growth factor α-mediated gastroprotection against stress ulceration in the rat: involvement of capsaicin-sensitive sensory neurons
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- 作者：Vongthavaravat ; Verapan ; Mesiya ; Sikandar ; Saymeh ; Layth ; Xia ; Yang ; Ward ; Angela ; Harty ; Richard F.
- 关键词：TGFα ; Gastroprotection ; Sensory neuron
- 刊名：Life Sciences
- 出版年：2003
- 出版时间：March 7, 2003
- 年：2003
- 卷：72
- 期：16
- 页码：1803-1811
- 全文大小：122 K
文摘
Exogenously administered TGFα has been shown to protect rodent gastric mucosa against injury caused by acid-dependent and acid-independent injury. The present study examined whether the gastroprotective effects of TGFα on stress-induced gastric ulceration in the rat involves activation of capsaicin-sensitive sensory neurons. Fasted male SD rats were subjected to water restraint stress (WRS) for four hours. Thereafter, rats were euthanized; the stomach opened and macroscopic areas of gastric ulceration quantitated (mm2). Gastric tissue contents of TGFα and the sensory neuropeptide, calcitonin gene-related peptide (CGRP) were determined by radioimmunoassay. Prior to stress rats received TGFα 50, 100 or 200 μg/kg by intraperitoneal injection. Sensory denervation was accomplished by high dose capsaicin treatment. WRS caused severe ulceration in the gastric corpus; 46.1 + 6.6 mm2. Parenteral administration of TGFα caused dose-dependent reduction in gastric injury: 34.7 + 4.9 mm2 with 50 μg/kg (p < 0.05); 25.4 + 3.6 mm2 with 100 μg/kg (p < 0.001) and 9.4 + 0.8 mm2 with 200 μg/kg (p < 0.001). The gastroprotective action of TGFα (200 μg/kg, i.p.) was abolished by capsaicin-induced sensory denervation. In addition, WRS ulceration was associated with significant reduction in gastric CGRP (−42 % ) and TGFα (−48 % ) content. Reduction in CGRP content was prevented by TGFα pretreatment. We conclude that: 1) TGFα caused dose-dependent gastroprotection against WRS ulceration, 2) TGFα-mediated gastric mucosal protection was prevented by capsaicin-induced sensory denervation and, 3) stress-induced injury was associated with significant reduction in gastric content of both TGFα and CGRP.