Dopamine as a novel anti-migration factor of vascular smooth muscle cells through D1A and D1B receptors.
To elucidate the roles of rat vascular dopamine D1A and D1B receptors in vascular smooth muscle cell migration, the effect of antisense oligonucleotides to D1A receptors (+1 to +21 of rat D1A receptors) and to D1B receptors (-12 to +6 of rat D1B receptors) on dopamine-mediated suppression of platelet-derived growth factor BB-mediated vascular smooth muscle cell migration, evaluated by the Boyden's chamber method, was studied. Increased vascular smooth muscle cell migration by platelet-derived growth factor BB (5 ng/ml) was suppressed significantly by co-incubation with dopamine (0.025-10 micromol/l) (by 15-59%). This suppression by 10 micromol/l dopamine was reversed by D1A antisense oligonucleotides (46%) and D1B antisense oligonucleotides (51%), but by neither the sense nor the random sense oligodeoxynucleotides to these receptors. The suppression by antisense oligodeoxynucleotides (21-51%) is dose dependent (1-10 micromol/l) and time dependent (0-4 h). Dopamine (10 micromol/l)-induced cyclic AMP formation is also suppressed by D1A antisense oligonucleotides (50%) and D1B antisense oligonucleotides (58%), but by neither the sense nor the random sense oligodeoxynucleotides to these receptors. The platelet-derived growth factor BB (5 ng/ml)-mediated activation of phospholipase D and protein kinase C activities were significantly suppressed by co-incubation with 10 micromol/l dopamine, which was reversed by D1A antisense oligonucleotides (45%) and D1B antisense oligonucleotides (50%) but by neither the sense nor the random sense oligodeoxynucleotides to these receptors. These results suggest that vascular D1A and D1B receptors inhibit migration of vascular smooth muscle cells, possibly through cyclic AMP activation and the suppression of phospholipase D and protein kinase C activities.
Yasunari
Kenichi
K
Department of Cardiology, Graduate School of Medicine, Osaka City University, Osaka, Japan. yasunari@osaka.med.or.jp
Maeda
Kensaku
K
Nakamura
Munehiro
M
Yoshikawa
Junichi
J
D000818:Animals; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D050641:Receptors, Dopamine D5
C493607:Drd5 protein, rat; D016376:Oligonucleotides, Antisense; D017447:Receptors, Dopamine D1; C098593:dopamine D1A receptor; D050641:Receptors, Dopamine D5; D004298:Dopamine