title: Heterologous down-regulation of vascular atrial natriuretic peptide receptors by phorbol esters.
abstract: Using cultured rat vascular smooth muscle cells (VSMC), the effect of protein kinase C activation on rat atrial natriuretic peptide (rANP) receptors and its effector system was studied. Tetradecanoyl phorbol acetate (TPA) induced a time- and temperature-dependent decrease of 125I-rANP binding to VSMC. TPA and phorbol dibutyrate inhibited the binding in a dose-related manner, whereas biologically inactive beta-phorbol was ineffective. Pretreatment of VSMC with TPA resulted in a marked reduction (50-70%) of rANP binding capacity without a significant change of its binding affinity. TPA pretreatment also induced attenuation of rANP-induced cGMP generation without affecting its basal levels. These data suggest that protein kinase C may be involved in the mechanism of heterologous down-regulation of vascular ANP receptors/guanylate cyclase system.
authors.affiliation: Hypertension-Endocrine Division, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D010703:Phorbol Esters; D010704:Phorbols; D011956:Receptors, Cell Surface; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D017461:Receptors, Atrial Natriuretic Factor; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol