Preliminary data developed in our laboratory indicate that the control of secretory function of the rat submandibular gland (SMG) changes as a function of developmental age. The prenatal SMG has the capacity to secrete but the typical stimulus - secretion coupling found in the adult gland is absent. It is hypothesized that secretory function of cells in the rat SMG in the perinatal period is regulated by different mechanisms than secretory function in the adult rat SMG. It is the purpose of the proposed study to investigate and define these differences in the regulation of secretion between the perinatal and adult SMG and to define the developmental timing of the transition from one type of secretion control to the other. The release of secretory peroxidase, sialic acid or (3H)-leucine (prelabelled) proteins in an in vitro lobule system will be used to evaluate the secretory response of perinatal SMG rudiments and adult tissue to various secretory stimuli (isoproterenol, norepinephrine, phenylephrine, dibutyryl cyclic AMP, 8-bromo cyclic GMP, pilocarpine, calcium-ionophore A23187). Direct measurements of alpha- and beta-adrenergic receptors and muscarinic cholinergic receptors will be performed on perinatal glands of differing ages. These studies will be correlated with electrophysiologic experiments to define the relationships between changes at the level of the secretory cells with development of neural regulation of secretion in vivo. These studies will be performed as a function of the developmental age of the animal to define the timing and nature of the changes in secretion control of the rat SMG. This approach to this problem will allow: (1) a definition of those factors which regulate secretion in the perinatal SMG, (2) a definition of the time course of the transition from the perinatal mechanisms for secretion control to the regulation of secretion found in the adult gland, (3) a developmental analysis of the cell surface receptors associated with secretion by the rat SMG, and (4) a total picture, correlating cell surface receptors, secondary message molecules and function in vitro and in vivo of the development of secretory function in the rat SMG.
