Delineation of the role of the autonomic nerves and receptors in regulation of secretion from, and growth of, parotid and submaxillary glands of adult and immature rat, as well as transport in perfused main duct of submaxillary continues to be the principal objectives; role in precursor fluid formation will be sought, using nerve stimulation for the first time. Responses mediated by activation of Alpha 1, Alpha 2, Beta 1 and Beta 2 adrenergic receptors during electrical stimulation of the sympathetic innervation to the glands will be studied by administering specific Alpha 1, Alpha 2, Beta 1 and Beta 2 antagonists in conjunction with nerve stimulation. Radioligand binding and specific Alpha 1, Alpha 2, Beta 1 and Beta 2 agonists will be used to identify active receptor populations. Premature or retarded development of autonomic receptors and nerves, secretory function, and cell maturation will be induced in the neonate by pharmacologic, surgical, and dietary manipulations. These should result in changes in number of specific receptors, possibly a shift from one kind to another, or a change in their ratios, or enhanced or retarded secretory development including glandular ability to accumulate electrolytes (as calcium). Electrical stimulation as well as chemical measurements are used to assess capability of nerves to respond. Secretory responses will be measured by determining concentration of such moieties as calcium, Cl, Na, K and amylase in the saliva or perfusate (with duct), or, when fluid is not obtainable measuring changes in glandular levels of these moieties following nerve or agonist-induced stimulation. Size of the adult glands will be regulated by the same manipulations that act to increase or decrease neurally-mediated activity (surgical denervation, gland ablation, feeding bulk or liquid diet, large doses of specific agonists) in the immature rat. In addition, effects of other size-regulating agents, such as Substance P and thyroxine, will be tested by measurement of glandular DNA and RNA and by cytological examination. The validity of the present concept regarding formation of precursor fluid will be tested using micropuncture of submaxillary gland during stimulation of the parasympathetic or sympathetic nerve to the gland on experimentally enlarged glands. This, and the studies on nerve and receptor mediated control of secretory and reabsorptive processes in main submaxillary duct, will provide a better understanding of the steps by which saliva is formed and secreted. Understanding of cause of cystic fibrosis may also result from this work.
