Cholinergic regulation of hamster pulmonary neuroendocrine cell calcitonin

The lung content of the peptide hormone calcitonin (iCT) has been localized to discrete and clustered pulmonary neuroendocrine cells. We have undertaken a study of the effect of the autonomic ganglionic agent nicotine on the iCT of hamster lung. The acute subcutaneous administration of nicotine raised serum iCT, while lung tissue concentration of the hormone changed reciprocally to that of the serum. One week following right-sided vagotomy, total (left plus right side) iCT levels decreased following nicotine; the concentration of iCT on the denervated right lung was more markedly decreased than that from the left lung. Hamster serum levels of iCT were significantly reduced following thyroid ablation. As in the intact animals, the subsequent subcutaneous injection of nicotine to these animals raised serum iCT. Further pharmacological evaluations revealed that subcutaneously administered nicotinic cholinergic antagonists, but not muscarinic cholinergic antagonists, prevented the nicotine-evoked increase in serum iCT. Furthermore, the subcutaneous injection of acetylcholine was found to mimic the effect noted for nicotine; this was also abolished by prior administration of a nicotinic antagonist, but not by a muscarinic antagonist. The present study suggests that the nicotinic effect on pulmonary iCT secretion is ganglionically mediated, presumably via vagal innervation of the pulmonary neuroendocrine cells.