MUSCLE CONTRACTION IN HUMAN & PRAIRIE DOG GALLBLADDERS
人体肌肉收缩
基本信息
- 批准号:3228276
- 负责人:
- 金额:$ 20.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1980
- 资助国家:美国
- 起止时间:1980-09-01 至 1995-03-31
- 项目状态:已结题
- 来源:
- 关键词:antihypercholesterolemic agent aspirin biological signal transduction calcium flux cholelithiasis cholesterol diacylglycerols disease /disorder prevention /control gallbladder human subject human therapy evaluation inositol phosphates isoleucine muscle contraction muscle relaxation norepinephrine obesity protein kinase C second messengers smooth muscle squirrel vasoactive intestinal peptide
项目摘要
DESCRIPTION: (Adapted from the applicant's abstract) Lithogenic bile
saturated with cholesterol is thought to contribute to gallbladder
hypomotility, but the mechanism whereby cholesterol damages the gallbladder
smooth muscle is not known. Human and prairie-dog gallbladders exposed to
cholesterol-saturated bile exhibit impaired contraction in response to
agonists. This abnormal response precedes the formation of gallstones.
Therefore, the investigators propose to characterize the signal
transduction pathways mediating contraction and relaxation in gallbladder
muscle from man and prairie dog and to determine the abnormalities induced
by exposure of gallbladder muscle to bile saturated with cholesterol.
First, the investigators will define transduction pathways utilized by
normal gallbladder muscle in response to agonists. The investigators will
examine the sources of calcium and the second messengers (1,4,5-inositol
triphosphate(IP3)-calmodulin or diacylglycerol-protein kinase C) utilized
by these agonists.
Next, the investigators will determine whether exposure of the muscle to
the excess cholesterol in bile causes disruption of specific transduction
pathway(s). Preliminary data suggest that cholesterol-induced damage may
be initially limited to the membrane, since cholesterol-damaged human
gallbladder muscle, after permeabilization with saponin, contracts normally
in response to IP3. The investigators will confirm this preliminary
finding with IP3 and examine whether the protein kinase C-dependent pathway
is similarly involved.
The investigators will then explore the various possible mechanisms
underlying relaxation in the gallbladder muscle. In this context the
investigators will examine the roles of norepinephrine, vasoactive
intestinal peptide, and peptide histidine isoleucine as possible
neurotransmitters mediating gallbladder relaxation in man and prairie dog.
The investigators will determine the relative role of increases in cAMP and
cGMP, and/or decreases in IP3 in inducing relaxation, and determine whether
any of these second messengers is affected by exposure to
cholesterol-saturated bile.
The investigators will test in prairie dogs whether cholesterol-induced
impairment of contraction is progressive, preventable, or reversible with
either ursodeoxycholic acid (UDCA), which solubilizes cholesterol, or with
aspirin, which may indirectly prevent formation of gallstones by inhibiting
prostaglandin synthesis. The results of these experiments, they believe,
may provide a rationale for treating overweight patients with impaired
gallbladder contraction and cholesterol microcrystals with UDCA.
These data, they believe, may elucidate the pathogenic role of cholesterol
in disrupting gallbladder contraction and may ultimately contribute to
long-term, nonsurgical treatment of patients with cholesterol stones.
描述:(改编自申请人摘要)产石胆汁
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOSE BEHAR其他文献
JOSE BEHAR的其他文献
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{{ truncateString('JOSE BEHAR', 18)}}的其他基金
Role of Progesterone in Colonic Muscle Dysfunction
黄体酮在结肠肌肉功能障碍中的作用
- 批准号:
6989786 - 财政年份:2004
- 资助金额:
$ 20.6万 - 项目类别:
Role of Progesterone in Colonic Muscle Dysfunction
黄体酮在结肠肌肉功能障碍中的作用
- 批准号:
6849229 - 财政年份:2004
- 资助金额:
$ 20.6万 - 项目类别:
Role of Progesterone in Colonic Muscle Dysfunction
黄体酮在结肠肌肉功能障碍中的作用
- 批准号:
7331463 - 财政年份:2004
- 资助金额:
$ 20.6万 - 项目类别:
Role of Progesterone in Colonic Muscle Dysfunction
黄体酮在结肠肌肉功能障碍中的作用
- 批准号:
7163438 - 财政年份:2004
- 资助金额:
$ 20.6万 - 项目类别:
Role of Progesterone in Colonic Muscle Dysfunction
黄体酮在结肠肌肉功能障碍中的作用
- 批准号:
6725171 - 财政年份:2004
- 资助金额:
$ 20.6万 - 项目类别:
STUDIES ON THE SPHINCTER OF ODDI AND GALLBLADDER
ODI 括约肌和胆囊的研究
- 批准号:
3228278 - 财政年份:1980
- 资助金额:
$ 20.6万 - 项目类别:
STUDIES ON THE SPHINCTER OF ODDI AND GALLBLADDER
ODI 括约肌和胆囊的研究
- 批准号:
3228277 - 财政年份:1980
- 资助金额:
$ 20.6万 - 项目类别:
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