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: 2750525
• 负责人: Jerry M. Farley
• 金额: $ 16.76万
• 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/2750525
• 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（根据申请人的摘要和具体目的改编）：哮喘 其特征在于气道平滑肌对痉挛原的超敏反应 （乙酰胆碱（ACh）、组胺（HIS）等）。这背后的原因 超敏反应未知。 促痉挛剂增加细胞内Ca 2 + 通过从肌浆中释放Ca 2+来调节[Ca 2 +]i 网织膜（SR），去极化和Ca 2+内流通过电压激活 通道和受体操作的通道。 Ca 2+的瞬时释放 SR为激活级联事件提供触发， 最终导致跨桥循环和张力发展。 涌入 细胞外Ca ~（2+）似乎参与了SR Ca ~（2+）的再填充 储备和张力维持。 β-肾上腺素受体激动剂，作用于b2 受体，诱导气管平滑肌细胞超极化，减少 Ca 2+内流和[Ca 2 +]i以及舒张。 该项目的目标是 表征信号转导通路之间的相互作用 由β-肾上腺素受体和痉挛素乙酰胆碱（ACh）激活， 组胺（HIS）在离体猪气管平滑肌细胞中作用。 的 具体目标是：1）检查KCa和KATP通道在 离体猪气管膜电位（Vm）和[Ca ~（2+）]i的调节 平滑肌细胞; 2）表征和比较痉挛原诱导变化 [Ca ~（2+）]i的变化以及这些效应对β-肾上腺素受体激活的调节; 3)表征参与SR Ca 2+库再填充的途径; 4)确定β-肾上腺素受体激活对 非受体介导的IP 3诱导的[Ca 2 +]i振荡;和5）检查 L-型钙通道受促痉挛剂和β-肾上腺素受体调节 刺激.