Figure 103

The role of diacylglycerol (DAG) and inositol triphosphate (Ins 1,4,5 P3) as second messengers linked to agonist-receptor (a±-adrenoceptor) interactions. Ptdins 4,5 P2 is a phosphatidylinositol precursor in cell membranes that is hydrolyzed following receptor activation to form the two second messengers, Ins 1,4,5 P3 and DAG. Once liberated within the cell, these second messengers activate separate but interacting pathways. Ins 1,4,5 P3 releases Ca++ stored in cells and can be phosphorylated to form a tetraphosphate (Ins 1,3,4,5 P4), which can open Ca++ channels in the membrane. DAG triggers protein phosphorylation through the activation of protein kinase C. Ca++-induced activation of the enzyme calmodulin also phosphorylates protein. Adenylyl cyclase traverses the membrane. Cyclic AMP-dependent protein kinase can phosphorylate and inactivate the (3-adrenoceptors. This kinase may have a role in homologous desensitization of Gs-protein-coupled (3-adrenoceptors. (3-Receptor stimulation can (1) activate Ca++ channels through an action of Gs proteins without the participation of cAMP and (2) affect other ion channels through phosphorylation via kinases. (Modified from Berridge MJ. Inositol triphosphate and diacylglycerol: Two interacting second messengers. ISI Atlas of Science: Pharmacology, 1:91, 1987.)

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