Regulation of pancreatic exocrine function: a role for cell-to-cell communication?
The effect of heptanol, an alkanol which decreases gap junctional permeability, was investigated in the perfused rat pancreas. Under basal conditions, heptanol (3.5 mM) caused a three- to fourfold increase of pancreatic juice, protein, and amylase outputs. The effect on enzyme secretion was fully reversible upon removal of the alkanol and was not secondary to the release of acetylcholine from nerve endings, since it was not prevented by addition of atropine (10(-6) M) to the perfusate. By contrast, another alkanol, hexanol (3 mM), which does not decrease coupling between acinar cells in spite of anesthetic properties analogous to those of heptanol, did not alter pancreatic secretion. The effect of heptanol was not mediated by a significant stimulation of cyclic AMP, nor did the alkanol increase the secretion of lactic dehydrogenase, a cytosolic marker. Analysis of the numerical density of freeze-fractured and immunolabeled gap junctions between acinar cells did not show differences between heptanol-perfused and control pancreases. In addition, heptanol did not alter carbachol (10(-6) M and 10(-5) M)-evoked amylase release. Since heptanol blocks cell coupling, apparently without interfering with the main intracellular pathways triggering enzyme release, we suggest that downregulation of direct cell-to-cell communications increases pancreatic exocrine secretion. Thus, cell coupling is probably involved in the regulation of the secretory activity of acinar cells.
D000438:Alcohols / Q000494:pharmacology; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D019850:Heptanol; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000438:Alcohols; D019850:Heptanol