Chew C S, Nakamura K, Ljungström M
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495.
Yale J Biol Med. 1992 Nov-Dec;65(6):561-76; discussion 621-3.
Gastric hydrochloric acid (HCl) secretion is stimulated in vivo by histamine, acetylcholine, and gastrin. In vitro studies have shown that histamine acts mainly via a cAMP-dependent pathway, and acetylcholine acts via a calcium-dependent pathway. Histamine also elevates intracellular calcium ([Ca2+]i) in parietal cells. Both gastrin and acetylcholine release histamine from histamine-containing cells. In humans, rats, and rabbits, there is considerable controversy as to whether or not gastrin receptors are also present on the parietal cell. We utilized digitized video image analysis techniques in this study to demonstrate gastrin-induced changes in intracellular calcium in single parietal cells from rabbit in primary culture. Gastrin also stimulated a small increase in [14C]-aminopyrine (AP) accumulation, an index of acid secretory responsiveness in cultured parietal cells. In contrast to histamine and the cholinergic agonist, carbachol, stimulation of parietal cells with gastrin led to rapid loss of the calcium signaling response, an event that is presumed to be closely related to gastrin receptor activation. Moreover, different calcium signaling patterns were observed for histamine, carbachol, and gastrin, Previous observations coupled with present studies using manganese, caffeine, and ryanodine suggest that agonist-stimulated increases in calcium influx into parietal cells do not occur via voltage-sensitive calcium channels or nonspecific divalent cation channels. It also appears to be unlikely that release of intracellular calcium is mediated by a muscle or neuronal-type ryanodine receptor. We hypothesize that calcium influx may be mediated by either a calcium exchange mechanism or by an unidentified calcium channel subtype that possesses different molecular characteristics as compared to muscle, nerve, and certain secretory cell types such as, for example, the adrenal chromaffin cell. Release of intracellular calcium may be mediated via both InsP3-sensitive and -insensitive mechanisms. The InsP3-insensitive calcium pools, if present, do not appear, however, to possess ryanodine receptors capable of modulating calcium efflux from these storage sites.
胃盐酸（HCl）分泌在体内受组胺、乙酰胆碱和胃泌素刺激。体外研究表明，组胺主要通过依赖cAMP的途径起作用，而乙酰胆碱通过依赖钙的途径起作用。组胺还可提高壁细胞内的钙浓度（[Ca2+]i）。胃泌素和乙酰胆碱均可从含组胺的细胞中释放组胺。在人类、大鼠和兔子中，壁细胞上是否存在胃泌素受体存在很大争议。在本研究中，我们利用数字化视频图像分析技术来证明胃泌素诱导的原代培养兔单个壁细胞内钙的变化。胃泌素还刺激[14C] -氨基比林（AP）积累略有增加，这是培养壁细胞酸分泌反应性的一个指标。与组胺和胆碱能激动剂卡巴胆碱不同，用胃泌素刺激壁细胞会导致钙信号反应迅速丧失，这一事件被认为与胃泌素受体激活密切相关。此外，观察到组胺、卡巴胆碱和胃泌素具有不同的钙信号模式。先前的观察结果以及目前使用锰、咖啡因和ryanodine的研究表明，激动剂刺激导致钙流入壁细胞增加并非通过电压敏感性钙通道或非特异性二价阳离子通道。细胞内钙的释放似乎也不太可能由肌肉或神经元型ryanodine受体介导。我们推测钙流入可能由钙交换机制或一种未确定的钙通道亚型介导，该亚型与肌肉、神经和某些分泌细胞类型（如肾上腺嗜铬细胞）相比具有不同的分子特征。细胞内钙的释放可能通过对肌醇三磷酸（InsP3）敏感和不敏感的机制介导。然而，如果存在对InsP3不敏感的钙池，它们似乎不具有能够调节这些储存部位钙流出的ryanodine受体。
