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.
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Authors | K Yasunari, M Kohno, H Kano, T Hanehira, M Minami, J Yoshikawa |
Journal | Clinical and experimental pharmacology & physiology. Supplement
(Clin Exp Pharmacol Physiol Suppl)
Vol. 26
Pg. S36-40
(Apr 1999)
ISSN: 0143-9294 [Print] Australia |
PMID | 10386252
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Dopamine Agonists
- Isoquinolines
- Platelet-Derived Growth Factor
- Receptors, Dopamine D1
- Tetrahydroisoquinolines
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
- zelandopam
- Dopamine
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Topics |
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
(pharmacology)
- Animals
- Arteriosclerosis
(etiology, prevention & control)
- Cell Division
(drug effects)
- Cell Movement
(drug effects)
- Dopamine
(pharmacology)
- Dopamine Agonists
(pharmacology)
- Hypertrophy
(etiology, prevention & control)
- Isoquinolines
(pharmacology)
- Muscle, Smooth, Vascular
(drug effects)
- Platelet-Derived Growth Factor
(drug effects)
- Receptors, Dopamine D1
- Tetrahydroisoquinolines
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