US-United Kingdom Cooperative Research: Role of Calcitonin Gene-Related Peptide in Pig Thydoid

该奖项将支持卡里博士与 德克萨斯大学医学分支的库珀和安东尼·凯尔博士， 英国利兹大学。研究人员建议研究 降钙素基因相关肽（CGRP）作为一种潜在 降钙素（CT）和其他分泌产物的促分泌素 猪甲状腺 CGRP是降钙素基因的替代产物， 在体内由神经元细胞广泛表达。 CGRP似乎 发挥重要的神经调节作用，控制神经功能 和血管张力，但它是否发挥内分泌调节 影响仍然未知。 库珀医生和凯尔会检查 降钙素基因相关肽对猪降钙素分泌有调节作用假说 甲状腺 在利兹大学，他们将在 手术分离猪甲状腺与CGRP及相关 通过甲状腺动脉注射多肽。 CT和其他甲状腺分泌物 将通过放射免疫测定法测量甲状腺中的分泌产物 静脉血浆 在德克萨斯大学医学分支， 将进行检测，研究人员将检查 猪甲状腺质膜CGRP的存在 受体。 放射性标记的CGRP将用于研究受体 通过经典的配体结合技术，以a）验证它们的 存在，B）估计它们的密度，c）检查 结合及其特异性，和d）检查灌注是否 甲状腺与CGRP结合导致其下调。 他们将 还检查含有受体的甲状腺膜，以确定 CGRP是否改变腺苷酸或鸟苷酸环化酶， 鉴定介导CGRP对CT作用的假定第二信使 分泌物 这些发现应该通过以下方式阐明这些机制： 这种新的肽CGRP可能调节甲状腺功能。

This award will support collaborative research between Dr. Cary Cooper, University of Texas Medical Branch, and Dr. Anthony Care, University of Leeds, England. The investigators propose to study the role of calcitonin gene-related peptide (CGRP) as a potential secretagogue of calcitonen (CT) and other secretory products in the pig thyroid gland. CGRP is an alternative product of the calcitonin gene and is expressed widely in the body by neuronal cells. CGRP appears to exert important neuromodulator actions to control nerve function and vascular tone, but whether it exerts endocrine regulatory effects remains unknown. Drs. Cooper and Care will examine the hypothesis that CGRP can regulate the secretion of CT from the pig thyroid gland. At the University of Leeds, they will perfuse the surgically isolated pig thyroid gland with CGRP and related peptides via the thyroid artery. Secretion of CT and other thyroid secretory products will be measured by radioimmunoassay in thyroid venous plasma. At the University of Texas Medical Branch, most of the assays will be conducted, and the investigators will examine pig thyroid gland plasma membranes for the presence of CGRP receptors. Radiolabeled CGRP will be used to study the receptors by classical ligand binding techniques in order to a) verify their presence, b) estimate their density, c) examine the kinetics of binding and their specificity, and d) examine whether perfusion of the thyroid with CGRP leads to their down-regulation. They will also examine receptor-containing thyroid membranes to determine whether CGRP alters adenylate or guanylate cyclase in an attempt to identify putative second messengers mediating the CGRP effect on CT secretion. The findings should shed light on the mechanisms by which this new peptide, CGRP, may regulate thyroid function.