CAMP STIMULATED SWEAT RATE IN CYSTIC FIBROSIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该项目的目标是开发一种循环amp （cAMP）刺激的“汗率”测试，该测试将区分完全功能、部分功能和非功能形式的囊性纤维化跨膜传导调节因子（CFTR）。胆碱能和胆碱能均可刺激汗液分泌；肾上腺素能受体激动剂。胆碱能刺激汗液的收集；随后测定汗液氯化物浓度是囊性纤维化（CF）标准诊断试验的基础，即匹罗卡品离子导入汗液试验。用匹罗卡品刺激汗液产生可导致汗腺初始产生等渗分泌。在非cf患者中，当分泌物穿过汗管时，氯化物被重新吸收，导致汗液中的氯化物浓度较低，因为它出现在皮肤上。这种氯化物的吸收依赖于功能性CFTR的存在。在缺乏功能性CFTR的CF患者中，汗液氯化物浓度仍然很高，amp；区分大多数（但不是全部）CF患者和非CF患者。然而，该技术不能区分CFTR突变的杂合子携带者和非携带者，汗液氯化物浓度也与疾病严重程度无关。假设camp介导的汗率测量将区分CF受试者、非CF受试者和未受CFTR突变影响的携带者。第二个假设是CFTR活性与排汗率之间存在相关性，因此未受CFTR突变影响的携带者对CF和非CF对照受试者的排汗率介于中间。另一个次要假设是，不同类型的CFTR突变可能与不同水平的出汗率有关。所有性别和年龄的受试者都有资格参赛。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is the development of a cyclic-AMP(cAMP)-stimulated "sweat rate" test that will discriminate between fully functional, partially functional, and non-functional forms of the Cystic Fibrosis Transmembrane Conductance Regulator(CFTR). Sweat production can be stimulated by both cholinergic amp; adrenergic agonists. Collection of cholinergic stimulated sweat amp; the subsequent measurement of sweat chloride concentration is the basis of a standard diagnostic test for cystic fibrosis (CF), the pilocarpine iontophoresis sweat test. Stimulation of sweat production with pilocarpine leads to initial production of an isotonic secretion in the sweat gland. In non-CF patients, as the secretion traverses the sweat duct, chloride is reabsorbed leading to low concentrations of chloride in sweat as it appears on the skin. This chloride resorption is dependent on the presence of functional CFTR. In CF patients, who lack functional CFTR, the sweat chloride concentration remains high, amp; distinguishes most, but not all, CF from non-CF patients. However, this technique does not distinguish heterozygote carriers of CFTR mutations from non-carriers, nor does the sweat chloride concentration correlate with disease severity. The hypothesis is that measurement of cAMP-mediated sweat rates will distinguish among CF subjects, non-CF subjects, and non-affected carriers of CFTR mutations. A secondary hypothesis is that there will be a correlation between CFTR activity and sweat rate such that non-affected carriers of CFTR mutations will have intermediate sweat rates to CF and non-CF control subjects. Another secondary hypothesis is that different classes of CFTR mutations can be associated with different levels of sweat rate. Subjects of both genders and all ages are eligible for entry.