PHYSIOLOGY OF THE ISOLATED MAMMALIAN PARIETAL CELL

酸分泌受多种化学递质的调节 通过血液和神经以及从局部组织库到达胃底粘膜。 这一更新建议是基于假设这些途径 调节胃酸分泌在胃底的多个点相互作用， 粘膜，在最终靶细胞和调节递送 内分泌/旁分泌递质。 这项建议的最广泛目标是 进一步描述了调节这些发射器的传递的因素， 受体的性质和位点以及介导 它们对壁细胞和生长抑素细胞的影响。 该方法是 还原法，酶法分离犬胃底粘膜细胞 治疗 细胞将通过速度和密度细胞技术分离 并使用各种免疫组织化学，内分泌， 生化标志物 胃泌素的双重作用，刺激顶叶 细胞和引起生长抑素的释放，强调的重要性， 描绘了抑制和刺激途径之间的相互作用。 因此，研究将集中在刺激因素（胃泌素和乙酰胆碱） 和抑制性成分[促甲状腺激素释放激素（TRH），表皮 生长因子（EGF）和生长抑素（Somatostatin）。 放射性配体技术，偶联 与放射自显影，将用于定位粘膜细胞上的受体， 每个发射器 受体表征将生物学 对这些递质的反应，主要研究壁细胞功能 (weak碱积累）和从细胞释放生长抑素 文化术语 介导刺激的机制和细胞元件， 将研究这些化学递质的抑制作用，重点是 钙和蛋白质以及受体磷酸化的作用。 这种方法 以及了解调节基因表达的因素 壁细胞的功能将通过发展技术 用于质膜受体的分离和表征。 本提案的长期目标是了解关键控制 正常生理学中的酸分泌机制， 酸性消化性疾病中酸分泌过多并影响对 治疗干预

Acid secretion is regulated by a myriad of chemical transmitters delivered to the fundic mucosa by blood and nerves and from local tissue stores. This renewal proposal is based upon the hypothesis these pathways regulating acid secretion interact at multiple points within the fundic mucosa, both at final target cells and modulating delivery of endocrine/paracrine transmitters. The broadest aim of this proposal is to further delineate the factors regulating delivery of these transmitters and the nature and locus of the receptors and cellular mechanisms mediating their effects on both parietal and somatostatin cells. The approach is reductionistic, isolating cells from canine fundic muocsa by enzyme treatment. Cells will be separated by velocity and density cell techniques and identified using a variety of immunohistochemical, endcrine, and biochemical markers. The dual effects of gastrin, to stimulate parietal cells and to cause the release of somatostatin, underline the importance of delineating the interactions between inhibitory and stimulatory pathways. Studies will thus focus on stimulatory elements (gastrin and acetylcholine) and inhibitory elements [thyrotropin releasing hormone (TRH), epidermal growth factor (EGF), and somatostatin]. Radioligand techniques, coupled with autoradiography, will be used localize receptors on mucosal cells for each of these transmitters. Receptor characterization will biological responses to these transmitters, primarily studying parietal cell function (weak base accumulation) and release of somatostatin from cells in short term culture. Mechanisms and cellular elements mediating stimulation and inhibition by these chemical transmitters will be studied, focusing on the role of calcium and protein and receptor phosphorylation. This approach and the potential for understanding the interplay of factors regulating parietal cell function will be greatly enhanced by developing techniques for isolation and characterization of the plasma membrane receptors. The long range goal of this proposal is to understand critical control mechanisms for acid secretion in normal physiology and as they relate to acid hypersecretion in acid peptic disease and influence the response to therapeutic intervention.