Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat
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Pathogenesis of indomethacin-induced gastric lesions was investigated in the rat by measuring lesions, gastric motility, and terminal blood glucose levels and correlating them with each other. Subcutaneously administered indomethacin (3–25 mg/kg) dose-dependently produced lesions in the stomach with concomitant gastric hypermotility and reduction of blood glucose levels. When the lesion score and the motility were plotted against terminal glucose levels, a highly significant relationship was found among these three factors (P < 0.01). Gastric lesions and hypermotility induced by indomethacin (25 mg/kg) were suppressed significantly by 16,16-dmPGE2 (10 Μg/kg) with no effect on the glucose levels, while intravenous infusion of glucose (25% w/w, 1.4 ml/hr) prevented these responses and restored the reduced glucose levels above the basal values. In addition, both 16,16-dmPGE2 and glucose infusion afforded a significant protection against gastric lesions induced by indomethacin even in the acid-perfused stomach (150 mM HCl). These results confirmed gastric hypermotility as a key element in the pathogenesis of indomethacin-induced lesions and further suggested that indomethacin may sensitize gastric contractility through glycoprivic receptors by inducing hypoglycemia and PG deficiency.
Key wordsindomethacin gastric lesion gastric motility blood glucose glycoprivic response
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