Ionic and osmotic dependence of secretion from permeabilised acini of the rat pancreas

Abstract

Many types of secretory granule have been observed to swell as a result of cell stimulation implying a degree of osmotic control, although the regulation of granule fusion with the apical plasma membrane is not clearly understood. In the present study we have investigated the ionic and osmotic dependency of basal and stimulated 3H-protein release from rat pancreatic acini, permeabilised by either digitonin or high voltage electric discharge. Acini were stimulated with either cholecystokinin-pancreozymin octapeptide (CCK-8), carbachol (CCh), or with phorbol ester (TPA) plus cAMP. Stimulated secretion was significantly reduced when 130 mmol/l Cl- in the buffer was replaced by I-, NO3-, SCN- or cyclamate-. Secretion in Cl- buffers was inhibited by the anion transport inhibitor 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), by 40% of the control response. Neither Na+ nor N-methyl-D-glucamine+ could replace K+ in the buffer. Ba2+ and quinine, which block K+ conductance pathways, inhibited stimulated secretion by 50%. Finally, stimulated secretion from leaky cells was nearly abolished by doubling buffer osmolarity. The data suggest that when the cell is stimulated, a Cl- and a K+ permeability appear in the zymogen granule membrane and the ions enter down their electrochemical gradients. The increased intragranular osmolarity results in granular swelling which is intimately associated with secretion.

Chloride Intracellular Channel Protein-4 Functions in Angiogenesis by Supporting Acidification of Vacuoles Along the Intracellular Tubulogenic Pathway

“…However, other possible roles for CLIC4 are not excluded. Chloride channels could also contribute to vesicle trafficking through mass transfer of salt into vesicles driving osmotic vesicle swelling, [33][34][35][36] although a necessary role for this process in general intracellular membrane traffic has never been proven. In addition, CLICs have been proposed to be involved in a variety of proteinprotein interactions.…”

Agonist-induced localized Ca2+ spikes directly triggering exocytotic secretion in exocrine pancreas.

“…Moreover, rises in C did notper se appear to affect G ( Figures 3B and C, and 4C). These results indicate that fusion of secretory granules evokes little insertion of active ion channels into the plasma membrane (Iwatsuki and Petersen, 1981), if any (Fuller et al, 1989 (Figures 2-4). Indeed, clear dissociation of AC and AG was found in three different experimental conditions.…”

Tmp21 and p24A, Two Type I Proteins Enriched in Pancreatic Microsomal Membranes, Are Members of a Protein Family Involved in Vesicular Trafficking

“…Zymogen granules were prepared from isolated acinar cells on a Percoll gradient as described (Fuller et al, 1989). * This study was supported by Grants SFB 246, B14 from the Deutsche Forschungsgemeinschaft.…”