title: Vanadate stimulation of adenylyl cyclase: an index of tyrosine kinase vascular effects.
abstract: BACKGROUND
  Beyond their mitogenic effects, hormones such as insulin, which activate receptor tyrosine kinases, regulate vascular tone. Further, we have demonstrated that receptor tyrosine kinase activation enhances adenylyl cyclase activation, a prominent mechanism that mediates vasodilation. However, whether tyrosine kinase-mediated human vascular responses parallel tyrosine kinase-mediated cellular effects on adenylyl cyclase activity is unknown.
  
  
  RESULTS
  To assess tyrosine kinase-mediated vascular responses, vascular sensitivity to insulin was assessed with the dorsal hand vein linear variable differential transformer technique. Insulin infusion resulted in a dose-dependent relaxation in all subjects. Cellular responses were assessed by means of the insulinomimetic vanadate-mediated sensitization of vascular adenylyl cyclase activity. Vanadate stimulated a tyrosine kinase-dependent enhancement of adenylyl cyclase function in human and rat aortic vascular smooth muscle cells, human lymphocytes, and human aortic endothelial cells. Further, maximal insulin-mediated vasodilation was significantly positively correlated with maximal vanadate-mediated enhancement of human lymphocyte adenylyl cyclase activity.
  
  
  CONCLUSIONS
  Insulin-mediated vasodilation is positively correlated with vanadate-mediated enhancement of adenylyl cyclase activity. Vanadate-mediated enhancement of adenylyl cyclase activity in lymphocytes may represent an index of tyrosine kinase-mediated vascular effects.
authors.affiliation: Department of Pharmacology, University of Western Ontario, John P. Robarts Research Institute, London, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Tan
authors.forename: C G
authors.initials: CG
authors.lastname: McDonald
authors.forename: J
authors.initials: J
authors.lastname: Chorazyczewski
authors.forename: A F
authors.initials: AF
authors.lastname: Burry
authors.forename: R D
authors.initials: RD
authors.lastname: Feldman
authors.forename: C J
authors.initials: CJ
authors.lastname: Macdonald
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006225:Hand / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D007328:Insulin; D014665:Vasodilator Agents; D005576:Colforsin; D014638:Vanadates; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases