title: Mechanisms involved in α1B-adrenoceptor desensitization.
abstract: α(1B)-Adrenergic receptors mediate many of the actions of the natural catecholamines, adrenaline and noradrenaline. They belong to the seven transmembrane domains G protein-coupled receptor superfamily and exert their actions mainly through activation of Gq proteins and phosphoinositide turnover/calcium signaling. Many hormones and neurotransmitters are capable of inducing α(1B)-adrenergic receptor phosphorylation and desensitization; among them: adrenaline and noradrenaline, phorbol esters, endothelin-I, bradykinin, lysophosphatidic acid, insulin, EGF, PDGF, IGF-I, TGF-β, and estrogens. Key protein kinases for these effects are G protein coupled receptor kinases and protein kinase C. The lipid/protein kinase, phosphoinositide-3 kinase also appears to play a key role, acting upstream of protein kinase C. In addition to the agents employed for cells stimulation, we observed that paracrine/autocrine mediators also participate; these processes include EGF transactivation and sphingosine-1-phosphate production and action. The complex regulation of these receptors unlocks opportunities for therapeutic intervention.
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. Ap. Postal 70-248, México, Distrito Federal. agarcia@ifc.unam.mx
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Romero-Ávila
authors.forename: Rocío
authors.initials: R
authors.lastname: Alcántara-Hernández
mesh_terms: D004815:Epidermal Growth Factor / Q000378:metabolism; D054768:G-Protein-Coupled Receptor Kinases / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D006728:Hormones; D008246:Lysophospholipids; D018377:Neurotransmitter Agents; D018340:Receptors, Adrenergic, alpha-1; C060506:sphingosine 1-phosphate; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D054768:G-Protein-Coupled Receptor Kinases; D013110:Sphingosine