DYNAMIC CALCIUM REGULATION IN AIRWAY SMOOTH MUSCLE

气道平滑肌的动态钙调节

基本信息

批准号：
6389611
负责人：
MATHUR S KANNAN
金额：
$ 22.51万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-04-01 至 2003-12-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6389611
关键词：
ADP ribosylation acetylcholine calcium channel calcium flux endothelin respiratory muscles sarcoplasmic reticulum smooth muscle tissue /cell culture

项目摘要

DESCRIPTION: Intracellular Ca2+ ([Ca2+]I) regulates a number of cellular processes in airway smooth muscle (ASM) in response to agonist stimulation. Recent studies from the principal investigator's laboratory indicate that agonists such as acetylcholine (Ach) and endothelin-1 induce [Ca2+]I oscillations in porcine ASM cells that reflect repetitive Ca2+ release through ryanodine receptor (RyR) channels of the sarcoplasmic reticulum (SR). Studies in non-smooth muscle tissue have demonstrated that cyclic ADP ribose (cADPR), metabolite of b-NAD, is a mediator for RyR activation. Preliminary studies related to this proposal also indicate that 1) cADPR is produced in ASM cells following agonist stimulation, 2) cADPR induces SR Ca2+ release through RyR channels, and 3) cADPR and its antagonist modulate agonist-induced [Ca2+]I oscillations. Additional studies also indicate that [Ca2+]I oscillations are frequency modulated in response to increasing agonist concentration as well as by cADPR. Slower Ca2+ -dependent cellular processes such as force production effectively integrate the faster [Ca2+]I oscillations. The overall hypothesis of the proposed studies is that cADPR, by affecting SR Ca2+ release through Ry channels, mediates agonist-induced [Ca2+]I oscillations in porcine ASM cells. The long-term goal of the proposed studies is to understand the signal transduction pathways underlying agonist-induced SR [Ca2+]I release in ASM cells. The proposed studies will determine the [Ca2+]I response to Ach and endothelin-1 stimulation in single ASM cells, and identify the role of cADPR i [Ca2+]I) regulation in ASM cells.

描述：细胞内Ca2+（[Ca2+] i）调节许多细胞气道平滑肌（ASM）的过程响应激动剂刺激。主要研究者实验室的最新研究表明激动剂，例如乙酰胆碱（ACH）和内皮素-1诱导[Ca2+] I 反映重复CA2+释放的猪ASM细胞中的振荡通过肌质网的Ryanodine受体（RYR）通道（SR）。在非平滑肌组织中的研究表明，环状ADP B-NAD代谢物核糖（CADPR）是RYR激活的介体。与该提案有关的初步研究还表明1）CADPR是激动剂刺激后在ASM细胞中产生的2）CADPR诱导SR CA2+通过RYR通道释放，3）CADPR及其拮抗剂调节激动剂引起的[Ca2+] I振荡。其他研究还表明 [Ca2+] I振荡是响应增加而调制的频率激动剂浓度以及CADPR。 Ca2+依赖性细胞较慢诸如力量产生之类的过程有效地整合了更快的[Ca2+] i 振荡。拟议研究的总体假设是CADPR，通过影响SR Ca2+通过RY通道释放，介导了激动剂诱导的 [Ca2+]猪ASM细胞中的I振荡。长期目标提出的研究是了解信号转导途径基础激动剂诱导的SR [Ca2+] I在ASM细胞中释放。提议研究将确定[Ca2+] I对ACH和内皮素-1的响应在单个ASM细胞中刺激，并确定CADPR I [Ca2+] i）的作用 ASM细胞中的调节。