Gastroprotective action of glucocorticoid hormones in rats with desensitization of capsaicin-sensitive sensory neurons.
The ability of glucocorticoid hormones to protect gastric mucosa during desensitization of capsaicin-sensitive afferent neurons has been investigated in rats. Functional ablation of the afferent neurons was performed by pre-treatment with neurotoxic doses of capsaicin (100 mg/kg s.c.). After 1 week of recovery, capsaicin-desensitized, as well as control rats were adrenalectomized or sham-operated. Seven days later, indomethacin at an ulcerogenic dose (35 mg/kg s.c.) was given to each group of rats. One half of adrenalectomized capsaicin-pre-treated rats were injected by corticosterone for replacement (4 mg/kg s.c., 15 min before indomethacin). Gastric lesions, plasma corticosterone and blood glucose levels were estimated 4 h after indomethacin administration. Indomethacin caused gastric erosions that were aggravated by adrenalectomy or desensitization of capsaicin-sensitive afferent neurons approximately with the same extension. Combination of adrenalectomy with the sensory desensitization profoundly potentiated the effect of sensory desensitization alone on indomethacin-induced gastric erosions: the mean gastric erosion area was increased approximately 10-fold. Corticosterone replacement completely prevented this profound effect of adrenalectomy. The results suggest a pivotal role of glucocorticoid hormones in the maintenance of gastric mucosal integrity in the case of impaired gastroprotective mechanisms provided by PGs and capsaicin-sensitive sensory neurons.
Bobryshev
P
P
Laboratory of Experimental Endocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, nab. Makarova, 6, St. Petersburg 199034, Russia.
Bagaeva
T
T
Filaretova
L
L
D000315:Adrenalectomy / Q000009:adverse effects / Q000379:methods; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005215:Fasting; D005753:Gastric Mucosa / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*; D013997:Time Factors
D001786:Blood Glucose; D005938:Glucocorticoids; D002211:Capsaicin; D007213:Indomethacin