Gastrin-histamine sequence in the regulation of gastric acid secretion.
Gastrin-histamine sequence in the regulation of gastric acid secretion.
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胃泌素-组胺序列在胃酸分泌调节中的作用。
作者：
H. Waldum;A. Sandvik;E. Brenna;H. Petersen
迷走神经在调节胃酸分泌中的重要性早在巴甫洛夫时代就已为人所知，“ 1905年艾德金斯假定胃窦激素胃泌素的存在”1920年，Popielsky描述了组胺刺激胃酸分泌因此，三种主要的酸性分泌剂乙酰胆碱（来自迷走神经）、胃泌素和组胺早就为人所知。迷走神经活动是由传入迷走神经和中枢神经系统调节的，胃泌素的释放是由胃液中的蛋白胨刺激的，而酸则抑制胃泌素的释放胃泌素的释放也受迷走神经活动的调节，可能是通过胃泌素释放肽生长抑素通过内分泌和旁分泌途径到达产生胃泌素的G细胞，也抑制胃泌素的释放另一方面，直到最近，对组胺释放的调节几乎完全不为人所知。20世纪60年代Kahlson等研究表明，食物，尤其是外源性胃泌素，在刺激组胺合成的关键酶组氨酸脱羧酶的同时，降低了氧合黏膜中组胺的含量，这表明组胺的释放是刺激酸分泌的重要步骤事实上，麦金塔“0和代码”先前已经提出，其他促分泌剂通过释放组胺来刺激酸分泌。后来Ekblad描述了乙酰胆碱对两栖动物氧合粘膜组胺释放的刺激作用。在最近的一篇综述中，Black和Shankley分析了不同分泌剂单独使用或与组胺阻滞剂联合使用的剂量反应曲线，并得出结论：胆碱能刺激释放组胺。“使用分离的血管灌注的大鼠胃，我们能够证明胃泌素能立即引起剂量依赖性的组胺释放。”我们之前研究了胃泌素和组胺浓度与胃酸分泌的关系，发现胃泌素不会增加最大组胺刺激的胃酸分泌。通过比较胃泌素对胃酸分泌的影响以及由此产生的胃静脉引流液中组胺的浓度5与组胺输注后的胃酸分泌反应6，很明显，胃泌素的促酸作用可能仅由组胺的释放来解释（图1）。在两种最高胃泌素浓度下，组胺释放量没有显著差异（图1），在后来的一项研究中，用葡聚糖代替白蛋白作为胶体，“在胃泌素浓度为520 pmolIl时，酸分泌和组胺释放量均达到最大值。”在这些研究中，我们使用磷酸二酯酶抑制剂异丁基甲基黄嘌呤（IBMX）来增加酸分泌。然而，IBMX并不影响组胺的释放。9我们还发现，生长抑素2和前列腺素E1类似物misoprostolF抑制胃泌素诱导的组胺释放和酸分泌，以及组胺刺激酸分泌。此外，胃泌素刺激的酸分泌和组胺释放严重依赖于细胞外钙浓度，而组胺刺激的酸分泌则不受影响。”对迷走神经的刺激导致组胺的释放，但其量不足以完全解释酸分泌的刺激。毒蕈碱受体1激动剂McN-A-343刺激酸分泌而不影响组胺释放，因此表明壁细胞上的毒蕈碱受体是M1型，而组胺产生细胞上没有。奇怪的是，胃泌素释放肽会轻微刺激胃酸分泌，同时抑制组胺的释放这种作用被生长抑素抗血清减弱，提示生长抑素释放可以解释胃泌素释放肽对组胺释放的抑制作用使用不同的组胺受体激动剂和拮抗剂，我们也能够证明组胺释放被修饰的H2受体抑制23大鼠体内酸分泌的调节如图2所示。因此，根据我们的结果，没有必要假设在大鼠壁细胞上存在胃泌素受体来解释胃泌素对酸分泌的刺激。胃泌素对产生组胺的肠染色质样细胞的特殊营养作用也使这些细胞极有可能具有胃泌素受体应该强调的是，在刺激功能和生长之间似乎普遍存在着密切的关系。27 .胃泌素对氧合粘膜的一般温和的回归性作用可能是由肠嗜铬细胞释放的物质介导的，如假定的胃钙素或组胺本身
The importance of the vagal nerves in the regulation ofacid secretion has been known since Pavlov,' and in 1905 Edkins postulated the existence of the antral hormone gastrin.' In 1920 Popielsky described stimulation of gastric acid secretion by histamine.3 Thus, the three major acid secretagogues acetylcholine (from the vagal nerves), gastrin, and histamine have been known for a long time. While vagal activity is regulated via afferent vagal nerves as well as by the central nervous system, gastrin release is stimulated by peptones in the gastric juice4 and is inhibited by acid.5 Gastrin release is also modulated by the vagal activity,6 possibly via gastrin releasing peptide.7 Somatostatin, which reaches the gastrin producing G cells via the endocrine as well as the paracrine pathways, also inhibits gastrin release.8 The regulation of histamine release, on the other hand, was almost completely unknown until recently. In the 60s, Kahlson et al showed that food, and especially exogenous gastrin, reduced the content of histamine in the oxyntic mucosa while stimulating the key enzyme in histamine synthesis, histidine decarboxylase, thus indicating that histamine release is an important step in the stimulation of acid secretion.9 In fact, MacIntosh"0 and Code" had previously suggested that the other secretagogues stimulated acid secretion by releasing histamine. Later on, Ekblad described the stimulation of histamine release by acetylcholine in amphibian oxyntic mucosa.'2 In a recent review Black and Shankley analysed the dose response curves for different secretagogues alone or with a histamine 2 blocker, and concluded that cholinergic stimulation releases histamine. '" Using isolated vascularly perfused rat stomach,'4 we were able to show that gastrin evokes an immediate and dose dependent histamine release."' We had previously studied the relation between the concentration of gastrin and histamine, and acid secretion and showed that gastrin does not augment maximal histamine stimulated acid secretion.'6 By comparing the effect ofgastrin on acid secretion and the resulting concentration of histamine in the gastric venous drainage'5 with the acid secretory response to histamine infusion,'6 it is evident that the acid stimulatory effect of gastrin may be explained solely by the release of histamine (Fig 1). There was no significant difference between the histamine release at the two highest gastrin concentrations (Fig 1), and in a later study'7 using dextran instead of albumin as colloid," both acid secretion and histamine release reached maximum at a gastrin concentration of 520 pmolIl. In these studies we used the phosphodiesterase inhibitor isobutyl methylxanthine (IBMX) to augment the acid secretion. IBMX, however, does not affect histamine release.'9 We have also shown that both somatostatin2' and the prostaglandin E1 analogue misoprostolF' inhibit gastrin induced histamine release and acid secretion as well as histamine stimulated acid secretion. Moreover, gastrin stimulated acid secretion and histamine release are heavily dependent on the extracellular calcium concentration, in contrast to histamine stimulated acid secretion which is unaffected." Stimulation of the vagal nerves resulted in a release of histamine in insufficient amounts to explain completely the stimulation of acid secretion. '" The muscarinic1 agonist McN-A-343 stimulates acid secretion without affecting histamine release, thus suggesting that the muscarinic receptor on the parietal cell, but not on the histamine producing cell, is of the M1 type. "9 Curiously, gastrin releasing peptide slightly stimulates acid secretion while concomitantly inhibiting histamine release.22 This effect is attenuated by somatostatin antiserum, suggesting that somatostatin release could explain the inhibitory effect of gastrin releasing peptide on histamine release.22 Using different histamine receptor agonists and antagonists, we were also able to show that histamine release is inhibited by a modified H2 receptor.23 The regulation of acid secretion in the rat is illustrated in Figure 2. According to our results, therefore, it is not necessary to postulate the presence of a gastrin receptor on the rat parietal cell to explain the stimulation ofacid secretion by gastrin. The specific trophic effect of gastrin on the histamine producing enterochromaffin like cells also makes it highly likely that these have a gastrin receptor.24 It should be stressed that there generally seems to be a close relation between the stimulation of function and growth.25"27 The moderate general tropic effect of gastrin on the oxyntic mucosa may be mediated by substances released from the enterochromaffin like cell such as the postulated gastrocalcin2' or histamine itself.29
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DOI：
10.1152/ajpgi.1982.242.5.g504
发表时间：
1982
期刊：
The American journal of physiology
影响因子：
--
作者：
Chew,CS;Hersey,SJ
通讯作者：
Hersey,SJ
胃底生长抑素对胃酸分泌的旁分泌调节。
DOI：
10.1152/ajpgi.1987.252.4.g485
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Schubert,ML;Edwards,NF;Arimura,A;Makhlouf,GM
通讯作者：
Makhlouf,GM
DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Gerber,JG;Barnes,JS
通讯作者：
Barnes,JS
分离的犬壁细胞上的胃泌素受体。
DOI：
10.1172/jci111348
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Soll,AH;Amirian,DA;Thomas,LP;Reedy,TJ;Elashoff,JD
通讯作者：
Elashoff,JD
DOI：
10.1152/ajpgi.1988.254.1.g40
发表时间：
1988
期刊：
The American journal of physiology
影响因子：
--
作者：
Soll,AH;Toomey,M;Culp,D;Shanahan,F;Beaven,MA
通讯作者：
Beaven,MA