Susceptibility to the development of gastric mucosal damage in OLETF rat not expressing the CCK-A receptor.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a new model of a congenital defect of the CCK-A receptor gene and should be useful for determining CCK-A receptor function. Since the CCK-A receptor plays an important role in gastrointestinal function, in the present study we examined, using OLETF rats, the hypothesis that a defect of the CCK-A receptor may influence gastric mucosal integrity. The gastric mucosal integrity was evaluated by the severity of gastric mucosal damage induced by ulcerogenic manipulations. The severity of gastric mucosal lesions seen after administration of intracisternal thyrotropin-releasing hormone analogue, subcutaneous indomethacin, intragastric HCl, or intragastric ethanol was evaluated in OLETF and control LETO rats. Administration of thyrotropin-releasing hormone analogue, indomethacin, HCl, or ethanol significantly increased the severity of gastric mucosal lesions in OLETF rats compared with control LETO rats. These results suggest for the first time that gastric mucosal integrity may be impaired in OLETF rats. It is furthermore speculated that individuals that lack of CCK-A receptors are highly susceptible to gastric ulceration.