Intracellular osmotic events accompanying protein secretion by the exocrine pancreas
Ho, J.J.; Rothman, S.S.
American Journal of Physiology 238(4): G289-G297
1980
ISSN/ISBN: 0002-9513 PMID: 6155078 Document Number: 163767
When the rabbit pancreas in vitro is stimulated with a cholinergic drug, there is a reciprocal inhibition of the secretion of new (labeled) vs. old (unlabeled) protein. This may be the result of the mobilization of unlabeled digestive enzyme from storage pools in the cytosol before secretion that in turn led to a competitive inhibition in the secretion of labeled protein. This model proposed a transient buildup of secretory protein in the cytosol soon after cholinergic stimulation. One prediction of such an occurrence is that, due to the infusion of osmoles into the cytosol, a transient flow depression might occur concurrent with the reciprocal inhibition. A dramatic transient depression in secretory flow does occur after cholinergic stimulation, which follows approximately the same time course as the reciprocal inhibition. Numerous other predictions were made and tested in an attempt to corroborate the hypothesis that the effect on flow was an osmotic consequence of the cytosolic passage of secretory protein. In each case, the prediction was supported by experimental observation. Preequilibration of the tissue in a medium of slightly raised or lowered osmolarity altered the extent and nature of the observed flow depression as predicted if a bolus of protein osmoles had been mobilized by the cholinergic agent. The osmotic effect was related to protein secretion by the observation that the greater the flow inhibition, the greater was the subsequent secretion of amylase, and by the fact that, although another stimulant of protein secretion had no effect on flow by itself, it both lessened the flow depression and reduced the rate at which amylase secretion initially increased after cholinergic stimulation. The stimulant-induced flow depression may be directly attributable to a transient osmotic gradient generated by an increase in the concentration of soluble digestive enzyme in the cytoplasm, derived presumably from zymogen granules.