Ding X Q, Kitano M, Håkanson R
Department of Pharmacology, University of Lund, Sweden.
Pharmacol Toxicol. 1998 Apr;82(4):177-82. doi: 10.1111/j.1600-0773.1998.tb01421.x.
Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.
胃泌素是一种具有重要生理意义的促分泌素。人们认为它通过动员胃底黏膜中肠嗜铬样（ECL）细胞释放组胺来间接刺激壁细胞。胃泌素通过作用于胆囊收缩素B/胃泌素受体来刺激ECL细胞的分泌活性和生长。已知急性阻断胆囊收缩素B/胃泌素受体可抑制胃泌素刺激的胃酸分泌，但持续阻断胆囊收缩素B/胃泌素受体是否会损害基础胃酸分泌、胃泌素和组胺刺激的胃酸分泌仍不确定。本研究旨在探讨长期（4周）阻断胆囊收缩素B/胃泌素受体对清醒大鼠基础胃酸分泌和刺激胃酸分泌的影响。通过渗透微型泵以3 μmol·kg⁻¹·hr⁻¹的剂量持续皮下输注选择性胆囊收缩素B/胃泌素受体拮抗剂YM022，给药时间从2小时至4周不等，对胃瘘大鼠进行给药。在治疗期间及停药后检测基础胃酸分泌、胃泌素和组胺刺激的胃酸分泌。在给药的4周期间，YM022对基础胃酸分泌和组胺刺激的胃酸分泌无影响，而胃泌素诱导的胃酸分泌受到抑制。YM022可使自由进食大鼠出现高胃泌素血症，但对禁食大鼠的血清胃泌素水平无影响。停药后3 - 7天，血清胃泌素浓度和胃泌素诱导的胃酸分泌恢复至对照水平。
