MUSCARINIC CONTROL OF GASTROINTESTINAL SMOOTH MUSCLE

毒蕈碱对胃肠平滑肌的控制

• 批准号: 3080603
• 负责人: JEFFREY L CONKLIN
• 金额: $ 7.48万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3080603
• 关键词: Anura; acetylcholine; adenylate cyclase; anticholinergic agent; beta adrenergic receptor; beta antiadrenergic agent; bioassay; calcium; chemical association; chemical binding; cholinergic agents; cyclic AMP; fresh water environment; gastrointestinal system; isoproterenol; ligands; muscarinic receptor; muscle contraction; neural information processing; scopolamine; smooth muscle; tritium

The contractile state of Gastrointestinal (GI) smooth muscle and therefore GI motor function are under the constant control of both excitatory and inhibitory neurohumoral influences. To fully understand normal and disordered GI motor function, it is essential to elucidate the mechanisms by which excitatory and inhibitory influences are integrated to control smooth muscle contraction. Studies using isolate smooth muscle cells (SMCs) have demonstrated that single SMCs possess both excitatory (muscarinic) and inhibitory (Beta-adrenergic) receptors, and that simultaneous signals from these receptors can be integrated at the level of the single cell. Previous studies have explored Beta-adrenergic inhibition of SMC contraction. The studies proposed here will use isolated SMCs from the stomach of Bufo marinus (marine toad) to elucidate the muscarinic receptor-agonist interactions responsible for initiating smooth muscle contraction, the changes in intracellular [Ca2+] produced by muscarinic receptor activation and the physiologic end response (contraction) produced by muscarinic receptor activation. This approach is unique since all of these processes can be assayed in intact SMCs under identical conditions, making direct correlations possible. A number of techniques including radioligand binding assays, assays of intracellular [Ca2+] concentration with quin2 and assays of SMC contraction with the Coulter counter will be done. In addition, these studies propose to study how SMCs integrate excitatory (muscarinic) and inhibitory (Beta-adrenergic) signals to produce a contractile response. Since intracellular free [Ca2+] and cAMP appear to be biochemical mediators responsible for altering SMC contractile state, I will explore how muscarinic and Beta-adrenergic receptor activation may interact to modulate these signals. Of particular importance is how Beta-adrenergic receptor activation and; therefore, increases in cAMP may influence intracellular free [Ca2+] in resting and muscarinic stimulate SMCs. These studies are designed to explore issues of great physiologic and therapeutic importance; that is how neurohumoral agents modulate smooth muscle function. Alterations in these control mechanisms may be responsible for such illnesses as diffuse esophageal spasm or idiopathic intestinal pseudoobstruction. By taking this unique approach, new and useful information will be obtained.

胃肠道（GI）平滑肌的收缩状态，因此 GI运动功能在兴奋性和 抑制性神经肿瘤的影响。 充分了解正常和 gi运动功能无序，必须阐明机制 通过哪些兴奋性和抑制作用进行整合以控制 平滑肌收缩。 使用分离平滑肌细胞的研究 （SMC）已经证明单个SMC具有两种兴奋性 （毒蕈碱）和抑制性（β-肾上腺素能）受体，并且 这些受体的同时信号可以集成在 单个单元格。 先前的研究探索了β-肾上腺素能抑制 SMC收缩。 这里提出的研究将使用来自 Bufo Marinus（海洋蟾蜍）的胃以阐明毒蕈碱 负责启动平滑肌的受体激动剂相互作用 收缩，毒蕈碱产生的细胞内[Ca2+]的变化 产生的受体激活和生理末端反应（收缩） 通过毒蕈碱受体激活。 这种方法是独一无二的 这些过程可以在相同条件下完整的SMC中测定 使直接相关性成为可能。 许多技术，包括 放射性结合测定，细胞内[Ca2+]浓度的测定 使用quin2和与库尔特计数器的SMC收缩的测定将是 完毕。 此外，这些研究建议研究SMC如何整合 兴奋性（毒蕈碱）和抑制性（β-肾上腺素能信号）产生 收缩回应。 由于无细胞内[CA2+]和营地似乎 成为负责改变SMC收缩状态的生化介质，我 将探讨毒蕈碱和β-肾上腺素能受体激活如何 互动以调节这些信号。 特别重要的是如何 β-肾上腺素能受体的激活和；因此，营地增加了 在静止和毒蕈碱刺激中影响细胞内无[Ca2+] SMC。 这些研究旨在探索出色的生理问题 和治疗重要性；这就是神经肿瘤剂调节光滑的方式 肌肉功能。 这些控制机制的改变可能是 负责弥漫性食管痉挛或特发性疾病 肠道假结构。 通过采用这种独特的方法，新的 将获得有用的信息。