title: Anti-atherosclerotic action of vascular D1 receptors.
abstract: 1. Vascular smooth muscle cell (VSMC) migration and proliferation are believed to play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1-like (D1 and D5) receptors in atherosclerosis, the effects of dopamine and the specific D1-like receptor agonists SKF 38393 and YM 435 on platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, proliferation and hypertrophy were investigated. 2. We observed that cell stimulated by 5 ng/mL PDGF-BB showed increased migration, proliferation and hypertrophy. These effects were prevented by co-incubation with dopamine, SKF 38393 or YM 435 at 1-10 mumol/L and this prevention was reversed by Sch 23390 (1-10 mumol/L), a specific D1-like receptor antagonist. These actions of D1-like receptor agonists were mimicked by 1-10 mumol/L forskolin, a direct activator of adenylate cyclase, and 0.1-1 mmol/L 8-bromo-cAMP. The actions were blocked by the specific protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulphonamide (H 89), but were not blocked by its negative control N-[2-(N-formyl-p-chlorocinnamylamino) ethyl]-5-isoquinoline sulphonamide (H 85). Platelet-derived growth factor-BB (5 ng/mL)-mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activity was significantly suppressed by co-incubation with dopamine. 3. These results suggest that vascular D1-like receptor agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly through the activation of PKA and the suppression of activated PLD, PKC and MAPK activity.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medical School, Japan. yasunari@cb3.so-net.or.jp
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: T
authors.initials: T
authors.lastname: Hanehira
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; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D006984:Hypertrophy / Q000209:etiology / Q000517:prevention & control; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines
chemical_list: D018491:Dopamine Agonists; D007546:Isoquinolines; D010982:Platelet-Derived Growth Factor; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C073504:zelandopam; D004298:Dopamine