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Our previous results demonstrate the gastroprotective but not ulcerogenic action of glucocorticoids released in response to ulcerogenic stress factors. The present study was undertaken to investigate the possible mechanisms underlying the gastroprotective action of glucocorticoids in rat stomachs. The effects of deficiency of glucocorticoid production, with or without corticosterone supplementation, on blood flow velocity in gastric microvessels, microvascular permeability, mucus production, motility as well as gastric lesions were studied 3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or indomethacin administration. The contribution of glucocorticoids in the healing process of gastric injury was also evaluated. The deficiency in glucocorticoid production significantly potentiated the functional disorders induced by ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus production and an increase in gastric motility and in microvascular permeability, which resulted in aggravation of the formation of gastric lesions as well as impairment of their healing. The changes observed were prevented by supplementation of corticosterone at a dose mimicking a stress-induced corticosterone rise. We conclude that a gastroprotective action of glucocorticoids may be provided by multiple actions, including maintenance of the gastric mucosal blood flow and mucus production, attenuation of the enhanced gastric motility and microvascular permeability as well as beneficial influences on healing processes.

The aim of the present work was to study the involvement of glucocorticoid receptors and corticotropin-releasing factor type 2 receptors (CRF-2 receptors) in mediating the analgesic effects of CRF on somatic pain sensitivity. The involvement of glucocorticoid and CRF-2 receptors in the development of analgesia evoked by systemic administration of CRF was studied by blockade of these receptors by their specific antagonists RU 38486 and astressin 2-B, respectively, in anesthetized rats. Pain sensitivity was tested before and 30 min after administration of CRF in terms of the threshold of the pain reaction induced by stimulation of the rat's tail with an electric current. Blockade of glucocorticoid receptors induced partial suppression of the analgesic action of CRF, while blockade of CRF-2 receptors produced complete suppression of the analgesic effect. These results provide evidence that glucocorticoid and CRF-2 receptors are involved in mediating the analgesic effects of CRF.

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Glucocorticoid hormones have dual action on the stomach: gastroprotective and ulcerogenic one. The present study was designed to investigate how physiological gastroprotective action of glucocorticoids can be transformed to pathological ulcerogenic effect. Dose- and time-dependent effects of single injection of dexamethasone on indomethacin-induced gastric erosions, corticosterone and blood glucose levels, somatic parameters were investigated in rats. Dexamethasone at the doses of 0.1, 1, 10 mg/kg decreased the gastric erosion area dose dependently in the case of its injection 1 h before indomethacin administration. Gastroprotective action of dexamethasone (at a dose of 1 mg/kg) was also observed in the case of its injection 6 and 12 h before indomethacin. However, the further increase in the time interval caused transformation of gastroprotective action of dexamethasone to ulcerogenic one. Accordingly to the data obtained short-term maintenance of blood glucose level provides the gastroprotective action of dexamethasone, while dexamethasone-induced long-lasting maintenance of blood glucose level accompanied with the signs of catabolic effects may be responsible at least partly for its ulcerogenic effect.

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.

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Glucocorticoids may have dual action on the gastric mucosa: gastroprotective and ulcerogenic. In this article, we review the data which suggested that an initial action of endogenous glucocorticoids, including stress-produced ones as well as exogenous glucocorticoids is gastroprotective and consider possible mechanisms of the conversion of physiological gastroprotective action of glucocorticoid hormones to their pathological ulcerogenic effect.