title: Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase.
abstract: Cyclic GMP (cGMP) mediates vascular smooth muscle relaxation in response to nitric oxide and atrial natriuretic peptides. One mechanism by which cGMP decreases vascular tone is by lowering cytosolic Ca2+ levels in smooth muscle cells. Although mechanisms by which cGMP regulates cytosolic Ca2+ are unclear, an important role for the cGMP-dependent dependent protein kinase in regulating Ca2+ has been proposed. Cyclic GMP-dependent protein kinase has been shown to regulate several pathways that control cytosolic Ca2+ levels: inositol 1,4,5-trisphosphate production and action, Ca(2+)-ATPase ATPase activation, and activation of Ca(2+)-activated K+ channels. The pleiotropic action of cGMP-dependent protein kinase is proposed to occur through the phosphorylation of important proteins that control several signaling pathways in smooth muscle cells. One potential target for cGMP-dependent protein kinase is the class of okadaic acid-sensitive protein phosphatases that appears to regulate K+ channels among other potentially important events to reduce cytosolic Ca2+ and tone. In addition, cytoskeletal proteins are targets for cGMP-dependent protein phosphorylation, and it is now appreciated that the cytoskeleton may play a key role in signal transduction.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham 35294.
authors.forename: T M
authors.initials: TM
authors.lastname: Lincoln
authors.forename: P
authors.initials: P
authors.lastname: Komalavilas
authors.forename: T L
authors.initials: TL
authors.lastname: Cornwell
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002455:Cell Division; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*
chemical_list: D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium