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Abstract

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.