Dynamics of protein and fluid secretion from the major salivary glands of rat: relevance of research findings to clinically observed defective secretion in cystic fibrosis.

Abstract

Although there are indications of a defect in secretion of protein from exocrine cells in cystic fibrosis (CF), this remains an aspect of CF research that has not been adequately addressed. Using salivary glands of rat as model systems, and following the effects of parasympathetic and sympathetic autonomic nerve stimulation on these glands, we demonstrate the existence of three separate pathways through which secretion of protein can be evoked from serous and mucous exocrine cells. These pathways allow the secretion of proteins from the intracellular compartments in a constitutive, intermediate or regulated manner. The primary aspects of secretory profile including concentration and the degree of hydration of secreted material differ greatly between the pathways, are cell type specific, and presumably are a direct consequence of controlled changes in the levels of second messengers induced upon stimulation of these cells. As previously published reports suggest that only the beta-adrenergic regulated pathway is affected by CF, differences between the pathways in their secretory profiles may influence the development of lung disease, through disparate disturbances in the secretion of protein and fluid from serous and mucous cells of the submucosal glands that line the bronchiolar tree in humans. We gratefully acknowledge support from The Wellcome Trust and from The European Union Biomed II Programme.