文摘
The participation of hypothalamus–pituitary–adrenal axis in the gastroprotective effects of nociceptin/orphanin FQ (N/OFQ) has been investigated. Gastric mucosal lesions were induced by intragastric administration of 50 % ethanol, 1 ml/rat. Rats received N/OFQ either by the intracerebroventricular (icv) route, at 3 µg/rat, or by the intraperitoneal (ip) route, at 10 µg/kg, 30 min before ethanol administration. The protective effect of icv and ip administered N/OFQ was assessed in adrenalectomized rats and in rats pretreated with the glucocorticoid receptor antagonist, mifepristone, or with the CRF receptor antagonist, α-helical CRF9–41. The damaging effect of ethanol was apparently not influenced by adrenalectomy. N/OFQ markedly reduced macroscopically and histologically assessed gastric mucosal damage. The extent of reduction by N/OFQ was comparable in adrenalectomized and in sham-operated rats, with either icv or ip route of administration. Pretreatment with mifepristone, both icv (80 µg/rat) and ip (10 mg/kg) injected, did not modify the response to icv and ip N/OFQ. Pretreatment with α-helical CRF9–41 (25 µg/rat icv or 250 µg/kg ip), had no effect on the reduction of gastric damage produced by icv or ip N/OFQ. Present findings suggest that the gastroprotective effects of N/OFQ on ethanol-induced damage do not involve the endocrine pathway through the HPA axis.
