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

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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.