title: IGF-I regulation of Na(+)-K(+)-ATPase in rat arterial smooth muscle.
abstract: Insulin-like growth factor I (IGF-I) is vasodilatory and mitogenic for vascular smooth muscle cells (VSMC). Alteration in VSMC Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity is hypothesized to underlie abnormal vascular tone and growth in hypertension and diabetes. Therefore, we investigated effects of IGF-I on Na(+)-K(+)-ATPase activity in rat aortic VSMC. IGF-I increases pump activity in a dose- and time-dependent manner: the minimal dose required was 10(-10) M, and the minimal time required was 20 min (at 10(-8) M) to increase activity. Similar effects persisted through 12 h. In Na(+)-loaded cells, IGF-I does not further stimulate activity. Blockade of Na+/H+ exchange attenuates IGF-I-induced increases in activity after 30 min but has no effect after 12 h. Northern blot analyses reveal that expression of the alpha 1- and the alpha 2-subunits of the pump were unaffected by IGF-I. Plasma membrane alpha 1- and alpha 2-protein were also unaffected, suggesting translocation of preformed pools was not responsible for the increases. Inhibitors revealed that neither tyrosine kinase activity, RNA transcription, protein synthesis, nitric oxide synthase activity, or protein kinase C activity mediated this IGF-I effect. Therefore, IGF-I regulates Na pump activity in the short term by an Na+/H+ exchange-dependent but transcription/translocation-independent mechanism. These data suggest that IGF-I, known to be produced by VSMC, may regulate tone and growth responses abnormal in disease states such as hypertension and diabetes.
authors.affiliation: Department of Physiology, Midwestern University, Glendale, Arizona 85308, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Standley
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: R M
authors.initials: RM
authors.lastname: Zayas
authors.forename: R
authors.initials: R
authors.lastname: Muniyappa
authors.forename: M F
authors.initials: MF
authors.lastname: Walsh
authors.forename: E
authors.initials: E
authors.lastname: Cragoe
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D007334:Insulin-Like Growth Factor I; D012964:Sodium; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D019331:NG-Nitroarginine Methyl Ester