title: Chloroquine inhibits alpha1B-adrenergic action in hepatocytes.
abstract: Noradrenaline increased phosphorylase a activity through activation of alpha1B-adrenoceptors in rat hepatocytes. Such effect was inhibited by chloroquine (Ki approximately 55 nM) and only slightly reduced by high concentrations of primaquine. Chloroquine did not inhibit the activation of phosphorylase a induced by vasopressin or angiotensin II. Binding competition experiments using [3H]prazosin showed that both chloroquine and primaquine interact with alpha1B-adrenoceptors, but only at very high concentrations. This indicates that the ability of chloroquine to block the alpha1B-adrenergic action was not due to antagonism at the receptor level. Noradrenaline increased phosphatidylinositol resynthesis and inositol trisphosphate production; these effects were inhibited by chloroquine and phorbol 12-myristate 13-acetate. Staurosporine and Ro 31-8220 (3-[1-[3-(amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3 -yl)maleimide), reduced the inhibitions induced by the active phorbol ester and the antimalarial drug on adrenergic-stimulated phosphatidylinositol resynthesis. Similarly, staurosporine blocked the inhibitory actions of chloroquine and phorbol 12-myristate 13-acetate on noradrenaline-stimulated inositol trisphosphate production. These data suggest the possibility that protein kinases, such as protein kinase C, could be involved in the actions of chloroquine.
authors.affiliation: Departimento de Bioenergetica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico. agarcia@ifcsun1.ifisiol.unam.mx
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sáinz
authors.forename: A
authors.initials: A
authors.lastname: Mendoza-Mendoza
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010762:Phosphorylase a / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010716:Phosphatidylinositols; D002738:Chloroquine; D011433:Propranolol; D010762:Phosphorylase a; D011494:Protein Kinases; D011493:Protein Kinase C; D009638:Norepinephrine