Dopamine D1-like receptor stimulation inhibits hypertrophy induced by platelet-derived growth factor in cultured rat renal vascular smooth muscle cells.
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.
Yasunari
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Kano
H
H
Yokokawa
K
K
Minami
M
M
Yoshikawa
J
J
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
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