Houi N, Kamisaki Y, Itoh T
Department of Clinical Pharmacology, Tottori University School of Medicine, Yonago, Japan.
Eur J Pharmacol. 1987 Nov 24;144(1):67-76. doi: 10.1016/0014-2999(87)90010-0.
Both the effect of imidazoline derivatives on acid secretion and the mechanism of this effect were studied in the parietal cells isolated from guinea pigs. Clonidine and tolazoline both stimulated the parietal cells to elevate the concentration of cyclic AMP and the accumulation of [14C]aminopyrine concentration dependently, although these imidazoline derivatives are known as alpha 2-adrenoceptor agonist or antagonist. These stimulatory effects were inhibited by famotidine, ranitidine and cimetidine, histamine H2 receptor antagonists. However, [3H]clonidine binding to the membrane preparations of parietal cells was not affected by these H2 antagonists and yohimbine but was inhibited by imidazoline derivatives. These results suggest that imidazoline derivatives may bind to the specific binding sites (different from H2 receptor or alpha 2-adrenoceptor) and stimulate the acid secretion of parietal cells with an increase of cyclic AMP, and that H2 antagonists may not only compete with the agonists for receptor binding but also interfere with the receptor adenylate cyclase system.
在从豚鼠分离出的壁细胞中研究了咪唑啉衍生物对胃酸分泌的影响及其作用机制。可乐定和妥拉唑啉均能刺激壁细胞，使环磷酸腺苷（cAMP）浓度和[14C]氨基比林蓄积量呈浓度依赖性升高，尽管这些咪唑啉衍生物分别被认为是α2肾上腺素能受体激动剂或拮抗剂。这些刺激作用被组胺H2受体拮抗剂法莫替丁、雷尼替丁和西咪替丁抑制。然而，[3H]可乐定与壁细胞膜制剂的结合不受这些H2拮抗剂和育亨宾的影响，但被咪唑啉衍生物抑制。这些结果表明，咪唑啉衍生物可能与特定结合位点（不同于H2受体或α2肾上腺素能受体）结合，并通过增加cAMP来刺激壁细胞的胃酸分泌，而且H2拮抗剂不仅可能与激动剂竞争受体结合，还可能干扰受体腺苷酸环化酶系统。
