Colombo M, Fort M, Farré A J
Department of Pharmacology, Laboratorios Dr. Esteve, S.A., Barcelona, Spain.
Methods Find Exp Clin Pharmacol. 1989 Oct;11(10):621-34.
The results of five different experiments carried out on isolated gastric mucosa were evaluated. These were: 1) Effects of antisecretory agents on (H+) and (K+) in a histamine-stimulated (4 x 10(-5)M) preparation. 2) Effects on (H+) in a preparation stimulated by dibutyryl cyclic adenosine monophosphate (dbcAMP) (6 x 10(-4)M). 3) Reversal by antipyrine (3 x 10(-2)M) of the antacid effect of antisecretory agents in a histamine-stimulated (4 x 10(-5)M) preparation. 4) Effects on the antacid activity of antisecretory agents of a pretreatment with 2-mercaptoethanol (2-ME) (2 x 10(-2)M) in a histamine-stimulated (4 x 10(-5] preparation. 5) Reversal by intraluminal increase of (K+) (up to 144.3 mM) of the antacid effect of antisecretory agents in a histamine-stimulated (4 x 10(-5)M) preparation. The technique and its application to a series of known antisecretory agents--cimetidine, ranitidine, timoprazole and omeprazole--and to other substances with antisecretory activity such as sodium thiocyanate, verapamil, trimipramine and imipramine, is described. In order to illustrate the activity of the aforementioned substances in the more classic tests of antisecretory activity, an in vivo test of inhibition of gastric secretion in pylorus-ligated rats and the in vitro tests of H2-receptor blocking activity (isolated guinea-pig atrium), anticholinergic activity (isolated guinea-pig ileum) and carbonic anhydrase (canine blood) were included. The results show that substances with different mechanisms of action behave differently in the five experiments in isolated gastric mucosa described, and these may thus be considered useful for the study of the mechanism of action of gastric antisecretory agents.
对在离体胃黏膜上进行的五项不同实验的结果进行了评估。这些实验包括：1）抗分泌剂对组胺刺激（4×10⁻⁵M）制剂中（H⁺）和（K⁺）的影响。2）对二丁酰环磷酸腺苷（dbcAMP）（6×10⁻⁴M）刺激制剂中（H⁺）的影响。3）在组胺刺激（4×10⁻⁵M）制剂中，安替比林（3×10⁻²M）对抗分泌剂抗酸作用的逆转。4）在组胺刺激（4×10⁻⁵）制剂中，用2-巯基乙醇（2-ME）（2×10⁻²M）预处理对抗分泌剂抗酸活性的影响。5）在组胺刺激（4×10⁻⁵M）制剂中，通过管腔内增加（K⁺）（高达144.3 mM）对抗分泌剂抗酸作用的逆转。描述了该技术及其在一系列已知抗分泌剂（西咪替丁、雷尼替丁、替莫拉唑和奥美拉唑）以及其他具有抗分泌活性的物质（如硫氰酸钠、维拉帕米、三甲丙咪嗪和丙咪嗪）中的应用。为了说明上述物质在更经典的抗分泌活性测试中的活性，纳入了幽门结扎大鼠胃分泌抑制的体内试验以及H₂受体阻断活性（离体豚鼠心房）、抗胆碱能活性（离体豚鼠回肠）和碳酸酐酶（犬血）的体外试验。结果表明，具有不同作用机制的物质在所述离体胃黏膜的五项实验中表现不同，因此这些实验可被认为有助于研究胃抗分泌剂的作用机制。
