The proposed project will deal with the cellular pharmacology of salivary secretion with in vitro parotid salivary gland preparations. An attempt will be made to delineate mechanisms by which receptors for hormones and neurotransmitters regulate second messengers such as Ca and cyclic AMP, and also mechaisms by which second messengers regulate cellular responses. A combination of biophysical, biochemical and morphological approaches will be used. Biophysical studies will include measurements of unidirectional and net fluxes of Ca++, Na+ and K+ ions. Biochemical studies will involve primarily measurement of phospholipid metabolism. Morphological studies, utilizing light ahd electron microscopy, will seek structural corelates of the biochemical and biophysical changes which drugs and neurotransmitters induce. Ultimately, unifying hypotheses may be developed describing the cellular and molecular mechanisms by which autonomic agents affect cell functions, and describing the cellular and molecular mechanisms of salivary secretion. Such information will prove useful in the future in a variety of health-related ways including: (1) the role of salivary secretion in dental health, (2) the understanding of basic exocrine functions as relevant to cystic fibrosis, and (3) understanding the molecular nature of autonomic receptors which regulate a variety of functions, including vascular reactivity, carbohydrate metabolism and CNS functions.
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