Saeki Y, Arakawa T, Higuchi K, Uno H, Watanabe T, Tominaga K, Nakamura S, Fukuda T, Nagura H, Kobayashi K
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S123-5.
Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered microcirculation due to vasoconstriction may cause gastric mucosal injury. In a previous study we found ET in gastric mucosal cells, especially chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was done to find whether ET affects G-cell function, particularly gastrin release and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. into 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, pirenzepin, or an intragastric pH of 2 on changes in the gastrin levels brought about by ET-1 were examined. The gastric contents of rats with the pylorus ligated were collected for 1 h and then for the next 4 h after the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immunostained 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 injection (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained for gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited the 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 microEq/h and 239 +/- 80 microEq/4 h, respectively) vs. controls (63 +/- 55 microEq/h and 346 +/- 81 microEq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduction of acidity.
内皮素（ET）是胃黏膜中一种强力的致溃疡物质。血管收缩导致的微循环紊乱可能会引起胃黏膜损伤。在先前的一项研究中，我们在胃黏膜细胞，尤其是主细胞和内分泌细胞以及血管内皮细胞中发现了ET。大多数对ET-1染色的内分泌细胞是G细胞。本研究旨在探究ET是否会影响G细胞功能，特别是胃泌素释放和胃酸分泌。将ET-1或ET-3（5 nmol/kg）静脉注射到雄性Wistar大鼠体内。在注射前以及注射后15、30或60分钟采集血样，并通过放射免疫分析法测定血清胃泌素水平。研究了ET受体拮抗剂BQ123-Na（伴宇）、哌仑西平或胃内pH值为2时对ET-1引起的胃泌素水平变化的影响。收集幽门结扎大鼠的胃内容物1小时，然后在注射ET-1后的接下来4小时内收集，计算胃酸分泌量。给予ET-1后，用抗胃泌素抗体对幽门腺区的胃黏膜进行免疫染色。ET-1注射后15、30和60分钟时的血清胃泌素水平（分别为220±94、204±77和366±191 pg/ml）显著高于注射前（75±18 pg/ml）。ET-1减少了胃泌素染色的细胞数量。ET-3对胃泌素水平无影响。BQ123-Na抑制了ET-1引起的胃泌素增加，但哌仑西平无此作用。在pH值为2时，ET-1对胃泌素无影响。与对照组（63±55微当量/小时和346±81微当量/4小时）相比，ET-1降低了胃酸分泌量（分别为2.6±2.3微当量/小时和239±80微当量/4小时）。因此，ET-1会增加大鼠血清胃泌素水平，这一作用可能与其酸度降低有关。
