title: Vascular dopamine-I receptors and atherosclerosis.
abstract: 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 receptors in atherosclerosis, the effects of dopamine, specific D1-like agonists SKF 38,393, and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC migration, proliferation, and hypertrophy were studied. We observed that cells stimulated by 5 ng/ml PDGF BB showed increased migration, proliferation and hypertrophy. These effects were prevented by coincubation with dopamine, SKF 38,393, or YM 435 at 1-10 mumol/l, and this prevention was reversed by Sch 23,390 (1-10 mumol/l), a specific D1-like antagonist. These actions are mimicked by 1-10 mumol/l forskolin, a direct activator of adenylate cyclase and 8-bromocyclic AMP at 0.1-1 mmol/l. The actions are blocked by a specific protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide (H 89), but are not blocked by its negative control, N-[2-(N-formyl-p-chlorocinnamylamino) ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/ml)-mediated activation of phospholipase D (PLD), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activity were significantly suppressed by coincubation with dopamine. These results suggest that vascular D1-like receptor agonists inhibit migration, proliferation and hypertrophy of VSMC, possibly through PKA activation and suppression of activated PLD, PKC and MAPK activity.
authors.affiliation: First Department of Internal Medicine, Osaka City University Medicial 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: D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D006801:Humans; D006984:Hypertrophy; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1