Delineation of the role of the autonomic nerves and receptors in regulation of growth and secretion, from submandibular and parotid glands of adult and immature rats, as well as transport in perfused main duct of submandibular gland continue to be main objectives. A new aspect includes delineation of the role of the peptides, nerve growth factor and epidermal growth factors (NGF AND EGF, respectively), that may affect neural regulation, either directly or indirectly. Beta agonist-induced growth does not occur unless one of these is present and the mechanism of this will be sought by administration of appropriate autonomic antagonists with NGF (EGF) and ISO, by partial sialadenectomy, or selective denervation. The cellular events, hyperplasia, hypertrophy, and activity of the growth-associated enzyme, beta galactosyltransferase will be assessed under these conditions, as well as following administration of growth factors alone. Premature or retarded development of autonomic nerves and receptors, secretory function, and cell maturation will be induced in the neonate by administration of growth factors, NGF and EGF; in addition, other pharmacologic, surgical, and dietary manipulations will be used to study neural control of these events. Electrical stimulation of the nerves will be used alone and in combination with selective autonomic antagonists to study the role of specific receptors and their subtypes on regulation of secretion of Na, K, C1, and amylase in adult and immature rat, and in regulation of transport of the ions in perfused main duct. Varying strength of stimulation will be done t vary amount of neurotransmitter released. This may permit resolution of contradictory findings, including neural regulation of amylase secretion. Secretion and radioligand binding studies of the denervated gland and main duct will permit correlation of development of supersensitivity in each (heretofore a particular glandular element has not been examined) with changes in number of receptors. All studies have the aim of providing a better understanding of the steps by which saliva is formed and secreted and the control by the classical neurotransmitters as well as the peptides mentioned.[3H] thymidine and [3H] uridine incorporation into DNA and RNA respectively will measure DNA and RNA synthesis; electrolytes will be measured by flame photometry or titration.
