Calcium in the regulation of aldosterone secretion and vascular smooth muscle contraction.
A model of angiotensin II action has been developed in which the flow of information from cell surface to cell interior proceeds by two temporally distinct branches: a calmodulin branch largely responsible for initiating the response; and a C-kinase branch for sustaining it. There are at least two initial events: a prompt and sustained increase in calcium influx rate, and prompt hydrolysis of phosphatidylinositol 4,5-bisphosphate. The latter leads to the generation of water-soluble inositol 1,4,5-trisphosphate and lipid soluble diacylglycerol. The rise in inositol 1,4,5-trisphosphate concentration causes the redistribution of intracellular calcium, a transient rise in the calcium concentration in the cytosol, and the activation of calmodulin-dependent enzymes, including protein kinase(s). As a result, several cellular proteins are rapidly phosphorylated and initiate the cellular response. The rise in calcium and these initial phosphorylation events are transient, however, so that an additional mechanism is necessary to sustain the response. The rise in diacylglycerol content, along with the transient rise in cytosolic calcium, leads to a shift of the C-kinase from a calcium-insensitive to a calcium-sensitive, plasma membrane-associated form. In this location, the activity of C-kinase is regulated by the rate of calcium flux across the plasma membrane. As a result of the activity of the C-kinase, a second set of cellular proteins becomes phosphorylated, and these control the sustained phase of the response.
Rasmussen
H
H
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Barrett
P
P
Takuwa
Y
Y
Apfeldorf
W
W
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D000242:Cyclic AMP / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism
D004075:Diglycerides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D000804:Angiotensin II; D000450:Aldosterone; D015544:Inositol 1,4,5-Trisphosphate; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium