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

该奖项将支持德克萨斯大学医学部的卡里·库珀博士和英国利兹大学的安东尼·凯尔博士之间的合作研究。研究人员建议研究降钙素基因相关肽(CGRP)在猪甲状腺中作为降钙素(CT)和其他分泌产物的潜在促分泌剂的作用。CGRP是降钙素基因的另一种产物，在体内由神经细胞广泛表达。CGRP似乎在控制神经功能和血管张力方面发挥着重要的神经调节作用，但它是否发挥内分泌调节作用尚不清楚。库珀博士和凯尔博士将检验CGRP可以调节猪甲状腺分泌CT的假说。在利兹大学，他们将通过甲状腺动脉向手术分离的猪甲状腺注入CGRP和相关多肽。CT和其他甲状腺分泌产物的分泌将在甲状腺静脉血浆中用放射免疫法测定。在德克萨斯大学医学分校，将进行大多数分析，研究人员将检查猪甲状腺质膜是否存在CGRP受体。放射性标记的CGRP将被用来通过经典的配体结合技术来研究受体，以便a)证实它们的存在，b)估计它们的密度，c)检查结合的动力学和它们的特异性，以及d)用CGRP灌流甲状腺是否导致它们的下调。他们还将检查含有受体的甲状腺膜，以确定CGRP是否改变腺苷或鸟苷环化酶，试图确定可能的第二信使，介导CGRP对CT分泌的影响。这一发现应该有助于阐明这种名为CGRP的新肽可能调节甲状腺功能的机制。

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.