Resting (basal) secretion of proteins is provided by the minor regulated and constitutive-like pathways and not granule exocytosis in parotid acinar cells

Resting secretion of salivary proteins by the parotid gland is sustained in situ between periods of eating by parasympathetic stimulation and has been assumed to involve low level granule exocytosis. By using parotid lobules from ad libitum fed rats stimulated with low doses of carbachol as an in vi tro analog of resting secretion, we deduce from the composition of discharg ed proteins that secretion does not involve granule exocytosis. Rather, it derives from two other acinar export routes, the constitutive-like (stimulu s-independent) pathway and the minor regulated pathway, which responds to l ow doses of cholinergic or P-adrenergic agonists (Castle, J, D,, and Castle , A. M. (1996) J, Cell Sci, 109, 2591-2599). The protein composition collec ted in vitro mimics that collected from cannulated ducts of glands given lo w level stimulation in situ. Analysis of secretory trafficking along the tw o pathways of resting secretion has indicated that the constitutive-like pa thway may pass through endosomes after diverging from the minor regulated p athway at a brefeldin A sensitive branch point. The branch point is deduced to be distal to a common vesicular budding event by which both pathways or iginate from immature granules. Detectable perturbation of neither pathway in lobules was observed by wortmannin addition, and neither serves as a sig nificant export route for lysosomal procathepsin B. These findings show tha t parotid acinar cells use low capacity, high sensitivity secretory pathway s for resting secretion and reserve granule exocytosis, a high capacity, lo w sensitivity pathway, for massive salivary protein export during meals, An analogous strategy may be employed in other secretory cell types.