MODULATORS OF GASTRIC HISTAMINE RELEASE IN VIVO

这项建议的目的是检查控制释放的因素 在狗体内的胃组胺。总体假设是 胃粘膜组胺受胃促分泌剂调节，而胃黏膜组织胺受胃促分泌剂调节 释放受抗分泌多肽和自体激素的调节。那只狗 是这些研究的正确模型，因为狗的胃粘膜 组织学在肥大细胞方面类似于人胃粘膜组织学 含有大量的粘膜组胺。拟议的目标将是 通过测量动脉和胃静脉血浆浓度来完成 组胺和1-甲基组胺穿过胃体 大多数含有组胺的肥大细胞和内分泌细胞 被控制住了。通过从胃静脉采集血液，排出胃体 测量胃和胃的血液流向胃体， 组胺的分泌率可以根据各种刺激进行计算。在……里面 此外，甲基组胺测量将允许评估 长时间输注促分泌剂期间的组胺代谢。通过 将化合物直接注入供应胃体的胃动脉 可以避免这些化合物对胃、全身的影响。组胺 甲基组胺将用气相色谱/负离子测定 化学电离质谱仪(GC/NICI-MS)。使用这项技术 在初步实验中，我们已经证明了五肽胃泌素输注 导致组胺和甲基组胺的释放大幅增加 胃部。该提案计划研究组胺释放的作用 在五肽胃泌素刺激的胃酸分泌方面也将有所探索。和 最后，将检查抗分泌化合物的能力 调节组胺的释放。这些化合物包括抗分泌物 多肽生长抑素、胰升糖素和分泌素；抗分泌性自体激素 前列腺素E2和I2，以及腺苷；交感神经刺激性异丙肾上腺素，以及 组胺-2激动剂，地马普特。这些实验应该 产生有关胃粘膜组胺控制的新信息 在完整的胃中释放。通过了解生理学和 胃粘膜组胺释放的药理控制 可以开发药理学方法来控制胃酸分泌。 消化性溃疡的治疗。

The aim of this proposal is to examine the factors controlling the release of gastric histamine in vivo in the dog. The overall hypothesis is that gastric mucosal histamine is regulated by gastric secretagogues, and the release is modulated by antisecretory polypeptides and autocoids. The dog is the correct model for these studies because dog gastric mucosal histology is similar to human gastric mucosal histology in that mast cells contain the bulk of the mucosal histamine. The proposed aim will be accomplished by measuring arterial and gastric venous plasma concentrations of histamine and 1-methyl histamine across the corpus of the stomach where most of the histamine-containing mast cells and endocrine cells are contained. By sampling blood from the gastric veins draining the corpus of the stomach and measuring gastric blood flow to the corpus of the stomach, histamine secretory rates can be calculated to various stimuli. In addition, methylhistamine measurements will allow the evaluation of histamine metabolism during prolonged infusion of secretagogues. By infusing compounds directly into the gastric artery supplying the corpus of the stomach, systemic effects of these compounds can be avoided. Histamine and methylhistamine will be measured by gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Using this technique in preliminary experiments, we have demonstrated that pentagastrin infusion results in a large increase in histamine and methylhistamine release from the stomach. The proposal plans to examine the role of histamine release in pentagastrin-stimulated acid secretion will also be explored. And finally, antisecretory compounds will be examined for their ability to modulate histamine release. These compounds include antisecretory polypeptides somatostatin, glucagon, and secretin; antisecretory autocoids prostaglandins E2 and I2, and adenosine; sympathomimetic isoproterenol,and the histamine-2 agonist, dimaprit. These sets of experiments should generate new information about the control of gastric mucosal histamine release in the intact stomach. By understanding the physiologic and pharmacologic control of gastric mucosal histamine release, another pharmacology approach can be developed to control acid secretion in the treatment of peptic ulcer disease.