Secretagogues activate chloride transport pathways in pancreatic zymogen granules

Abstract

The membrane permeability of pancreatic zymogen granules was evaluated in vitro with granules isolated from rats in different secretory states: 1) untreated, 2) pretreated with a muscarinic antagonist, 3) pretreated with a muscarinic and an adrenergic antagonist, 4) pretreated as in 3 and then stimulated with the secretagogue cholecystokinin 4 min before death, and 5) pretreated as in 3 and then stimulated with the secretagogue secretin 4 min before death. Granules isolated from untreated rats had variable ionic permeabilities but in general possessed both chloride conductance and electroneutral exchange pathways with low permeabilities to alkali metal ions. In contrast, granules from animals pretreated with secretory antagonists had very low ion permeabilities to both inorganic anions, such as chloride, and alkali metal ions. Injection of the peptide secretagogues cholecystokinin or secretin resulted in a relatively fast (within 4 min) activation or induction of high chloride permeabilities through both chloride conductance and chloride/hydroxide (or chloride/bicarbonate) exchange pathways. In addition, the secretagogues increased the cation permeability of the granule membrane, which exhibited a distinct potassium selectivity. Chloride conductance has been postulated to play a major role in fluid secretion coupled to exocytosis of macromolecules [R. C. DeLisle and U. Hopfer, Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G489-G496, 1986]. These results demonstrate that granules may actively participate in the secretory process and suggest that some of the physiological targets in the cascade of events leading to secretion are anion and cation transporters in the zymogen granule membrane.

Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

“…In mast cells, an increase in secretory vesicle volume after stimulation of secretion has been suggested from electrophysiological measurements (5). The requirement of osmotic force in the fusion of phospholipid vesicles with a membrane bilayer also has been demonstrated (6). Isolated zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas and parotid glands, possess Cl Ϫ and ATPsensitive, K ϩ -selective ion channels at the vesicle membrane, whose activities are implicated in vesicle swelling (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

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.…”

Regulation of the water channel aquaporin‐1: isolation and reconstitution of the regulatory complex

“…Studies using isolated ZGs from the exocrine pancreas and parotid glands demonstrate the presence of Cl and ATP-sensitive K + selective ion channels at the vesicle membrane, whose activities have been implicated in vesicle swelling (Fuller et al, 1989a,b;Gasser et al, 1988;Gasser and Hopfer, 1990;Segawa et al, 1991;Takuma et al, 1993;Thevenod et al, 1990Thevenod et al, , 1992Thevenod et al, , 1996. Furthermore, secretion of ZG contents in permeabilized pancreatic acinar cells requires the presence of both K + and Cl ions (Curran and Brodwick, 1991).…”