title: Dopamine D1-like receptor stimulation inhibits hypertrophy induced by platelet-derived growth factor in cultured rat renal vascular smooth muscle cells.
abstract: Vascular smooth muscle cell (VSMC) hypertrophy is believed to play some roles in atherosclerosis. To elucidate the role of vascular D1-like receptors in VSMC hypertrophy, the effects of dopamine and specific D1-like receptor agonists SKF 38393 and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC hypertrophy was studied. We observed that cells stimulated by PDGF-BB 5 ng/mL showed increased VSMC hypertrophy. These effects were prevented by coincubation with dopamine, SKF 38393, and YM 435 1-10 mumol/L, and this prevention was reversed by Sch 23390 1 to 10 mumol/L, a specific D1-like receptor antagonist. These actions are mimicked by forskolin 1 to 10 mumol/L, a direct activator of adenylate cyclase and 8-bromo-cAMP 0.1 to 1 mmol/L, and are blocked by a specific protein kinase A (PKA) inhibitor N-[2-(P-bromcoinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H89) but not blocked by its negative control. PDGF-BB (5 ng/mL)-mediated mitogen-activated protein kinase (MAPK) activity was significantly suppressed by coincubation with D1-like receptor agonists, which were reversed by PKA inhibitor H 89. These results suggest that vascular D1-like receptor agonists inhibit hypertrophy of VSMC, possibly through PKA activation and suppression of activated MAPK activity.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yasunari
authors.forename: M
authors.initials: M
authors.lastname: Kohno
authors.forename: H
authors.initials: H
authors.lastname: Kano
authors.forename: K
authors.initials: K
authors.lastname: Yokokawa
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: J
authors.initials: J
authors.lastname: Yoshikawa
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006984:Hypertrophy / Q000517:prevention & control; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000187:drug effects*; D012077:Renal Artery; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D007546:Isoquinolines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D017447:Receptors, Dopamine D1; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; D000077214:Becaplermin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C073504:zelandopam; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide