title: Insulin desensitized beta 1-adrenergic receptor-mediated stimulation of adenylyl cyclase in SK-N-MC cells.
abstract: Receptor cross-talk is an emerging field which investigates cross-regulation between distinct classes of receptors. In the present work, we investigated the influence of activating the insulin receptor, a tyrosine kinase receptor, on beta-agonist activation of adenylyl cyclase, which is mediated by a G protein-linked receptor. Treatment of SK-N-MC neuroepithelioma cells with insulin generated a marked attenuation of beta 1-adrenergic receptor-mediated stimulation of adenylyl cyclase. This effect required nanomolar concentrations of insulin, occurred within minutes of exposure of these cells to insulin, and did not result from down-regulation of beta-adrenergic receptors. Insulin alone reduced the maximal isoproterenol-mediated stimulation of adenylyl cyclase by 50%, while the co-addition of the phosphatase inhibitor sodium vanadate increased the magnitude of insulin inhibition to 90%. Insulin provides an additional avenue for heterologous desensitization of beta-adrenergic receptors and their transmembranal signalling pathway.
authors.affiliation: Department of Pharmacology, University of Tennessee, Memphis 38163.
authors.forename: S W
authors.initials: SW
authors.lastname: Bahouth
authors.forename: S
authors.initials: S
authors.lastname: Lopez
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology
chemical_list: D007328:Insulin; D011943:Receptors, Adrenergic, beta; D014638:Vanadates; D011972:Receptor, Insulin; D000262:Adenylyl Cyclases; D007545:Isoproterenol