The autonomic nervous system with its two antagonistic branches, the sympathicus and the parasympathicus, regulates the activities of all body functions that are not under voluntary control. While the autonomic regulation of organ functions has been extensively studied, little attention has been given to the potential role of neurohumoral transmission at the cellular level in the development of
cancer. Studies conducted by our laboratory first showed that binding of the parasympathetic
neurotransmitter,
acetylcholine, as well as
nicotine or its nitrosated
cancer-causing derivative, NNK, to
nicotinic acetylcholine receptors comprised of alpha7 subunits activated a mitogenic signal transduction pathway in normal and neoplastic pulmonary neuroendocrine cells. On the other hand,
beta-adrenergic receptors (Beta-ARs), which transmit signals initiated by binding of the
catecholamine neurotransmitters of the sympathicus, were identified by our laboratory as important regulators of cell proliferation in cell lines derived from human
adenocarcinomas of the lungs, pancreas, and breast. The tobacco-specific
carcinogen NNK bound with high affinity to Beta1- and Beta2-ARs, thus activating
cAMP, protein kinase A, and the
transcription factor CREB. Collectively,
neurotransmitter receptors of the nicotinic and Beta-
adrenergic families appear to regulate cellular functions essential for the development and survival of the most common human
cancers.