Neuroregulatory Aspects of Brain Calcitonin

降钙素是一种由哺乳动物甲状腺和鸟类和鱼类的多鳃腺体中的特殊细胞产生的多肽激素。在哺乳动物中，这种荷尔蒙被分泌到血液中，以应对血液中钙的升高。它传播到肾脏和骨骼，在那里作用于靶细胞，靶细胞通过增加肾脏钙排泄和减少骨骼分解来做出反应，从而将血钙降至正常水平。库珀博士已经证明，降钙素被引入中枢神经系统后会产生行为变化。事实上，这种多肽对食物和水的摄取、痛觉和胃酸分泌都有深远的影响。然而，降钙素并不是在大脑中自然存在的，循环中的降钙素无法通过血脑屏障。库珀博士认为，中枢神经系统中存在一种类似降钙素的分子，但尚未被确认，因为它与外周甲状腺激素产生的降钙素分子不同。他将使用降钙素的结构类似物来分离中枢神经系统受体，并确定是否存在不止一个亚型的降钙素受体。然后，库珀博士将比较中枢神经系统和外周降钙素受体的特性，以确定它们的异同。此外，他还将描述当被引入中枢神经系统时启动摄食、饮水和胃酸分泌的多肽序列。这项工作将增加我们对多肽如何在大脑中充当化学信使的一般理解。此外，这项工作对于开发用于止痛和胃酸分泌的药理药物具有潜在的实用价值。

Calcitonin is a peptide hormone produced by special cells in the mammalian thyroid gland and the ultimobranchial gland of birds and fish. In mammals, the hormone is secreted into the bloodstream in response to a rise in blood calcium. It travels to the kidney and bone where is acts on target cells that respond by enhancing renal calcium excretion and reducing bone breakdown, thereby lowering blood calcium back to normal. Dr. Cooper has shown that calcitonin produces behavioral changes when it is introduced into the CNS. Indeed, this peptide has profound effects on food and water intake, pain perception, and gastric acid secretion. Yet, calcitonin has not been found naturally in the brain, and circulating calcitonin cannot get through the blood-brain barrier. Dr. Cooper suggests that a calcitonin-like molecule is present in the CNS but has not been identified because it is different than the one produced in the periphery by the thyroid hormone. He will use structural analogs of calcitonin to isolate CNS receptors, and to determine whether more than one subtype of calcitonin receptor exists. Dr. Cooper will then compare the properties of the CNS and peripheral calcitonin receptors to determine their similarities and differences. In addition, he will characterize the peptide sequences that when introduced into the CNS initiate feeding, drinking and gastric acid secretion. This work will increase our general understanding of how peptides act as chemical messengers in the brain. Moreover, potential usefulness of this work for the development of pharmacological agents for pain control and gastric acid secretion is noted.