Mechanisms of α1-Adrenergic and Related Responses

Exton, John H.

doi:10.1007/978-1-4613-1915-3_4

Cited by 6 publications

(8 citation statements)

References 495 publications

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“…Evidence that agonists also promote the influx of Ca21' comes from electrophysiological studies and from comparisons of the changes in cytosolic Ca2 observed in the presence and absence of extracellular Ca21'. A role for Ca2" influx is also supported by measurements of early changes in 45Ca2"' uptake (4…”

Section: "mentioning

confidence: 78%

“…Ca2"' and a phospholipid (e.g., phosphatidylserine) for activity (37). DAG stimulates it by reducing its Ca21' requirement to the submicromolar range found in the cytosol (4,36). Tumor-promoting phorbol esters act similarly, and protein kinase C is believed to be the major cellular target of these compounds.…”

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

“…However, the cytosolic targets are often proteins of unknown function identified by gel electrophoresis. Because many effects of agonists are mimicked by phorbol esters or synthetic DAGs (4,36), it is likely that there are many physiologically important substrates for protein kinase C, but the majority of these remain to be defined.…”

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

“…In addition to exerting effects on receptors, protein kinase C can modify signal transduction at other sites, perhaps G proteins (4,36). This leads to modulation of agonist effects on adenylate cyclase and PIP2 hydrolysis (4, 5).…”

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

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Mechanisms of action of calcium‐mobilizing agonists: some variations on a young theme

Exton

1988

FASEB j.

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237

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It is now accepted that many hormones and neurotransmitters exert their effects through G protein-mediated activation of a phospholipase C, which breaks down phosphatidylinositol bisphosphate. This releases inositol trisphosphate, which mobilizes intracellular calcium, and diacylglycerol, which, in turn, activates protein kinase C. However, recent evidence indicates that other mechanisms are involved. In some cells, the increases in cytosolic calcium elicited within 1-2 s by high concentrations of agonists or at later times by low, physiological concentrations of agonists occur without any detectable changes in inositol phosphates and calcium mobilization, and result from the opening of plasma membrane channels that are permeable to Ca2+. This response appears to be mediated more directly by G proteins. These findings question the postulated roles of inositol phosphates and calcium mobilization in the stimulation of calcium influx. Measurements of the mass and fatty acid composition of the inositol phospholipids and of the diacylglycerol and phosphatidic acid generated by agonists in several cell types indicate that phosphatidylinositol bisphosphate is probably a minor source of these lipids. On the other hand, measurements of phosphatidylcholine, choline, and phosphocholine indicate that this phospholipid is a major source, and that its breakdown involves both phospholipase C and D. These findings indicate that phosphatidylcholine breakdown may be more important than phosphoinositide hydrolysis in the regulation of protein kinase C and perhaps other cell functions.

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Section: "mentioning

confidence: 78%

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

Section: Role Of Protein Kinase C In the Actions Of Ca2-mobilizing Agmentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of action of calcium‐mobilizing agonists: some variations on a young theme

Exton

1988

FASEB j.

Self Cite

237

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show abstract

“…However, in addition to Ca 2+ mobilization from internal stores agonists also stimulate Ca 2+ influx. This has been demonstrated by several studies that clearly distinguish influx from decreased efflux (e.g., unidirectional 45Ca 2+ flUX experiments [Exton 1987] and studies which monitor Mn 2+ quenching of fura2 fluorescence [Hallam et al 1988Merritt and Hallam 1989;Jacob 1990]). …”

Section: New Generation Of Ca2+-sensitive Fluorescence Indicatorsmentioning

confidence: 88%