Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat. Role of glycoprivic response.
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 less than 0.01). Gastric lesions and hypermotility induced by indomethacin (25 mg/kg) were suppressed significantly by 16,16-dmPGE2 (10 micrograms/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 sensitive gastric contractility through glycoprivic receptors by inducing hypoglycemia and PG deficiency.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Okada
M
M
Niida
H
H
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000172:deficiency*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000097:blood / Q000139:chemically induced
D001786:Blood Glucose; D005947:Glucose; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin