The role of phosphatidylinositides in stimulus-secretion coupling in the exocrine pancreas.
Cell activation of different cell types is accompanied by receptor-mediated stimulation of phospholipase C and a consequent breakdown of phosphatidylinositol 4,5-bisphosphate. Evidence suggests that GTP-binding proteins are involved in this signal transduction mechanism, which couples receptors to phospholipase C. Both the hydrolysis products diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP3) are intracellular messengers for cellular responses such as secretion, as illustrated by the pancreatic acinar cell. IP3 releases Ca2+ from a nonmitochondrial Ca2+ pool likely to be the endoplasmic reticulum (ER). This Ca2+ release leads to a transient rise in the cytosolic free Ca2+ concentration from approximately 100 to approximately 800 nmol/liter, by which enzyme secretion is initiated. For sustained secretion, Ca2+ influx into the cell is necessary to keep the cytosolic free Ca2+ concentration at a slightly elevated level. Activation of protein kinase C by DG and Ca2+ seems to play a major role in the second, sustained phase of secretion. Ca2+ reuptake into the ER and Ca2+ extrusion from the cell are achieved by (Ca2+ + Mg2+)-ATPase in both the ER and the plasma membrane as well as by an Na+/Ca2+ exchange in the latter. In the final step of exocytosis, protein phosphorylation by Ca2+-, DG-, and cAMP-dependent protein kinases is probably involved.
Schulz
I
I
Max-Planck-Institut für Biophysik, Frankfurt/Main, Federal Republic of Germany.
Schnefel
S
S
Banfić
H
H
Thévenod
F
F
Kemmer
T
T
Eckhardt
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000502:physiology; D010179:Pancreas / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D011494:Protein Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium