APICAL MEMBRANE TRAFFICKING DURING REGULATED PANCREATIC EXOCRINE SECRETION - ROLE OF ALKALINE PH IN THE ACINAR LUMEN AND ENZYMATIC CLEAVAGEOF GP2, A GPI-LINKED PROTEIN

The GP2/THP family of glycosyl phosphatidylinositol (GPI)-anchored pro teins is targeted to apical secretory compartments in polarized epithe lial cells. We demonstrate in the rat exocrine pancreas that enzyme-me diated release of GP2 from acinar cell membranes represents a pa-depen dent process regulated by bicarbonate secreted from ductular cells. Re lease of GP2 from secretin-stimulated pancreatic lobules, which retain intralobular ducts, was inhibited by (i) bicarbonate substitution, (i i) chloride substitution, and (iii) DIDS, a potent inhibitor of chlori de-bicarbonate exchange. These inhibitory effects were not observed in preparations of pancreatic acini devoid of ductal elements. Enzymatic cleavage of GP2 and amylase release from pancreatic acini varied dire ctly as a function of pH of the acinar lumen. Alkali-induced GP2 relea se could be correlated with ultrastructural and biochemical evidence f or stimulated retrieval (endocytosis) of exocytic membranes at the aci nar lumen, Our study defines functional roles for ductal bicarbonate i n acinar cell and lumen physiology and provides a potential explanatio n for the biological significance of enzyme-mediated cleavage of GP2 f rom the apical plasma membrane,