Участие гормонов гипоталамо-гипофизарно-адренокортикальной системы крыс в гастропротекции при сенситизации и десенситизации капсаицин-чувствительных афферентных нейронов

Abstract

The aim of this work was to study: a) the contribution of glucocorticoids to gastroprotection induced by sensitization of capsaicin-sensitive afferent neurons (CSN), b) gastroprotective effect of corticotropin-releasing factor (CRF) in rats with desensitization of CSN and possible corticosterone participation in this effect. The study was performed in male Sprague Dawley rats weighing 260-300 g. The immobilization at 10° C (3 h) or indomethacin (35 mg/kg) were used as ulcerogenic stimuli. Sensitization of CSN was induced by administration of capsaicin at the doses of 1 and 10 mg/kg, 1h before the onset of ulcerogenic stimulus. Desensitization was performed by administration of capsaicin in a total dose of 100 mg/kg (20+30+50) in 3 subsequent days, 2 weeks before the start of the experiment. CRF was injected at the dose of 2.5 mg/kg, i. p., 30 minutes before indomethacin in rats with CSN desensitization. To estimate the involvement of corticosterone in the gastroprotective effects, metyrapone (inhibitor of glucocorticoid synthesis) at the dose of 30 mg/kg was used. Capsaicin, administered at doses of 1 and 10 mg/kg, caused a gastroprotective effect in both ulcerogenic models. The metyrapone administration 30 minutes before capsaicin eliminated its gastroprotective effect for the 1 mg/kg dose, but not 10 mg/kg dose. The CRF administration caused a gastroprotective effect in both control rats, and rats with CSN desensitization. The results obtained in experiments with metyrapone indicate that CRF gastroprotective effect observed in rats with desensitization of CSN are at least partially mediated by corticosterone.