Neuroregulatory Aspects of Brain Calcitonin

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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.