REGULATION OF STRESS S-RELATED GENE EXPRESSION IN THE STOMACH

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Restraint and water-immersion stress rapidly induces heat shock protein 70 (HSP70) in rat gastric mucosa. When bilaterally adrenalectomized or subdiaphragmatically vagotomized rats were exposed to the stress, adrenalectomy completely abolished the stress-induced activation of heat shock factor 1 (HSF1). HSP70 mRNA expression, and HSP70 induction, while vagotomy enhanced them. These surgical manupulations did not change the HSF1 level in gastric mucosa. The extent of-the HSP70 induction correlated inversely with the severity of mucosal damage, suggesting an important role of HSP70 in the defense against stress ulcer. Intraperitoneal injection of epinephrine, but not norepinephrine nor dexamethasone, could induce HSP70 in the gastric mucosa of adrenalectomized rats. The stress-induced HSP70 induction in normal rats was inhibited by αィイD21ィエD2- and αィイD21AィエD2-adrenoceptor antagonists, leading to aggravate mucosal damage, while αィイD21B/1DィエD2-, αィイD22ィエD2- and β-adrenoceptor antagonists or a glucocorticoid receptor antagonist had no effect on the HSP70 induction and mucosal damage. Our results suggest that the stress-induced heat shock response of gastric mucosa may be under adrenergic regulation, possibly through the αィイD21AィエD2- adrenergic receptor.