B-RECEPTOR/SPASMOGEN INTERACTIONS--AIRWAY SMOOTH MUSCLE

B 受体/痉挛原相互作用——气道平滑肌

• 批准号: 2460175
• 负责人: Jerry M. Farley
• 金额: $ 16.28万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460175
• 关键词: acetylcholine; beta adrenergic receptor; bronchospasm; calcium channel; calcium flux; histamine; inositol phosphates; membrane potentials; muscle contraction; potassium channel; respiratory hypersensitivity; respiratory muscles; sarcoplasmic reticulum; smooth muscle; swine

DESCRIPTION (Adapted from applicant's abstract and specific aims): Asthma is characterized by hypersensitivity of airway smooth muscle to spasmogens (acetylcholine (ACh), histamine (HIS) etc.). The underlying cause of this hypersensitivity is unknown. Spasmogens increase cytosolic Ca2+ concentration ([Ca2+]i) through the release of Ca2+ from the sarcoplasmic reticulum (SR), depolarization, and Ca2+ influx through voltage-activated channels and receptor-operated channels. The transient release of Ca2+ from the SR provides the trigger for the activation of a cascade of events which ultimately lead to cross-bridge cycling and tension development. The influx of extracellular Ca2+ appears to be involved in the refilling of the SR Ca2+ stores and tension maintenance. beta-adrenoceptor agonists, acting at b2 receptors, induce tracheal smooth muscle cell hyperpolarization, a decrease in Ca2+ influx and [Ca2+]i, and relaxation. The goal of this project is to characterize the interactions between the signal transduction pathways activated by beta-adrenoceptors and the spasmogens acetylcholine (ACh) and histamine (HIS) in isolated tracheal smooth muscle cells from swine. The specific aims are to: 1) examine the role of KCa and KATP channels in the regulation of membrane potential (Vm) and [Ca2+]i in isolated swine tracheal smooth muscle cells; 2) characterize and compare spasmogen-induced changes in [Ca2+]i and the modulation of these effects on b-adrenoceptor activation; 3) characterize the pathways involved in the refilling of the SR Ca2+ store; 4) determine the effects of b-adrenoceptor activation on non-receptor-mediated IP3-induced oscillations in [Ca2+]i; and 5) examine the regulation of L-type Ca2+ channels by spasmogens and beta-adrenoceptor stimulation.

描述(根据申请者的抽象和具体目标改编)：哮喘 其特点是呼吸道平滑肌对痉挛原高度敏感 (乙酰胆碱(ACh)、组胺(His)等)。造成这种情况的根本原因是 过敏症是未知的。痉挛原增加胞内钙离子浓度 通过肌浆中钙离子的释放来浓缩([Ca2+]i) 网状结构(SR)、去极化和钙离子通过电压激活的内流 通道和受体控制的通道。钙离子的瞬时释放 SR为激活一系列事件提供触发器，这些事件 最终导致跨桥骑行和张力的发展。人流涌入 胞外Ca~(2+)似乎参与了肌质网钙离子的再充盈 商店和紧张关系的维护。β-肾上腺素能受体激动剂，作用于b2 受体，诱导气管平滑肌细胞超极化，减少 在Ca~(2+)内流和[Ca~(2+)]i，并松弛。这个项目的目标是 描述信号转导通路之间的相互作用 由β-肾上腺素受体和痉挛原乙酰胆碱(ACh)和 猪气管平滑肌细胞中的组胺(His)。这个 具体目的是：1)研究KCA和KATP通道在 猪离体气管膜电位和[Ca~(2+)]i的调节 平滑肌细胞；2)表征和比较痉挛原诱导的变化 [Ca~(2+)]i及这些效应对b-肾上腺素能受体激活的调节作用； 3)确定参与肌质网钙库再充盈的途径； 4)确定b-肾上腺素能受体激活对 非受体介导的IP3诱导的[Ca~(2+)]i振荡；5)检测 痉挛原和β-肾上腺素能受体对L钙通道的调节 刺激。