Stimulus-secretion coupling in pancreatic acinar cells.
Figure 4 summarizes the steps by which Ca2+ and cyclic AMP-mediated secretagogues activate enzyme secretion in the pancreatic acinar cell. CCK and acetylcholine bind to specific plasma membrane receptors and through an as yet incompletely understood mechanism give rise to an elevation in free cytoplasmic Ca2+. A question central to this scheme is whether receptor binding leads to intracellular Ca2+ mobilization through generation of a diffusable mediator. Clues to answering this question may come from a) determining whether Ca2+ is released from the plasma membrane in addition to one or more intracellular organelles, and b) examining the role (if any) of membrane phosphatidylinositol metabolism in Ca2+ mobilization. A second class of secretagogues, represented by VIP and secretin, bind to their specific receptors and cause the accumulation of cyclic AMP. Cyclic AMP potentiates Ca2+ in activating secretion, and in some species, cyclic AMP may activate secretion independently of Ca2+. Ca2+ may act by regulating the activity of calmodulin dependent protein kinase(s) and phosphatase(s) and a phospholipid dependent kinase (protein kinase C) which has also been shown to be activated by diacylglycerol; cyclic AMP activates a distinct kinase termed protein kinase A. These kinases and phosphatases then alter the phosphorylation of specific proteins which are presumed to play structural or regulatory roles in exocytosis. Potentiation may thus result from interaction of Ca2+ and cyclic AMP at the level of a protein kinase, phosphatase or protein substrate.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011817:Rabbits; D012633:Secretin / Q000494:pharmacology; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D002766:Cholecystokinin; D000242:Cyclic AMP; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; D000109:Acetylcholine; D002118:Calcium