Two Regulated Secretory Pathways for Newly Synthesized Parotid Salivary Proteins Are Distinguished by Doses of Secretagogues

Low doses of the muscarinic agonist pilocarpine (0.1-1 microM) and the beta-adrenergic agonist isoproterenol (0.5-4 nM) stimulate a minor regulated secretory pathway for salivary proteins in rat parotid lobules. Newly synthesized proteins (labeled biosynthetically) are selectively discharged, and they are secreted in the same relative proportions as observed in constitutive-like unstimulated secretion but different from the proportions of older proteins that are discharged by granule exocytosis in response to higher doses of secretagogue. The response to low doses of agonists is transient and involves output of no more than 1-2% of tissue-associated amylase. The same increase in output of pulse-labeled proteins is observed when agonist is added at various chase times (1.5-6 hours), implying that release occurs from a post-Golgi storage pool. Stimulation for 40 minutes significantly depletes the storage pool as a second stimulation elicits smaller output. Stimulation also partially depletes labeled proteins from subsequent constitutive-like secretion after the agonist is removed implying that the constitutive-like and low dose agonist mediated pathways draw on the same pool of secretory proteins. While these results indicate that acinar cells have a second regulated secretory pathway, this new pathway is unlikely to contribute uniquely to the protein composition of parotid secretion. Rather it may serve a different role in secretion at the apical cell surface.