EFFECTS OF ENDOTHELIN ON SERUM GASTRIN LEVEL AND ACID-SECRETION IN RATS

Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered mi crocirculation due to vasoconstriction may cause gastric mucosal injur y. In a previous study we found ET in gastric mucosal cells, especiall y chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was don e to find whether ET affects G-cell function, particularly gastrin rel ease and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. in to male Wistar rats. Blood samples were collected just before and 15, 30, or 60 min after injection and serum gastrin levels were assayed by RIA. The effects of BQ123-Na (Banyu), an ET receptor antagonist, pire nzepin, or an intragastric pH of 2 on changes in the gastrin levels br ought about by ET-1 were examined. The gastric contents of rats with t he pylorus ligated were collected for 1 h and then for the next 4 h af ter the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immu nostained with antigastrin. The serum gastrin levels at 15, 30, and 60 min after ET-1 injection (220 +/- 94, 204 +/- 77, and 366 +/- 191 pg/ ml, respectively) were significantly higher than those before the inje ction (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained fo r gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited th e increase in gastrin caused by ET-1, but pirenzepin had no effect. At pH 2, ET-1 had no effect on gastrin. ET-1 decreased acid output (2.6 +/- 2.3 mu Eq/h and 239 +/- 80 mu Eq/4 h, respectively) vs. controls ( 63 +/- 55 mu Eq/h and 346 +/- 81 mu Eq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduct ion of acidity.