Dopamine as a novel antimigration and antiproliferative factor of vascular smooth muscle cells through dopamine D1-like receptors.

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 and specific D1-like agonists SKF 38,393 and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC migration and proliferation were studied. We observed that cells stimulated by PDGF-BB (5 ng/mL), showed increased migration and proliferation. These effects were prevented by coincubation with dopamine, SKF 38,393, or YM 435 (1 to 10 mumol/L), and this prevention was reversed by Sch 23,390 (1 to 10 mumol/l), a specific D1-like antagonist. These actions are mimicked by forskolin (1 to 10 mumol/L), a direct activator of adenylate cyclase and 8-bromo-cAMP at 0.1 to 1 mmol/L and are blocked by a specific protein kinase A inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H 89), but not blocked by its negative control, N-[2-(N-formyl)-p-chlorociannamylamino)ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/mL)-mediated activation of phospholipase D, protein kinase C, and mitogen activated protein kinase activity were significantly suppressed by coincubation with dopamine. These results suggest that vascular D1-like receptor agonists inhibit migration and proliferation of VSMC, possibly through protein kinase A activation and suppression of activated phospholipase D, protein kinase C, and mitogen-activated protein kinase activity.

• Authors: K Yasunari, M Kohno, T Hasuma, T Horio, H Kano, K Yokokawa, M Minami, J Yoshikawa
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 17 Issue 11 Pg. 3164-73 (Nov 1997) ISSN: 1079-5642 [Print] United States
• PMID: 9409307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agonists
• Dopamine Antagonists
• Enzyme Inhibitors
• Growth Inhibitors
• Isoquinolines
• Naphthalenes
• Platelet-Derived Growth Factor
• Proto-Oncogene Proteins c-sis
• Receptors, Dopamine D1
• Sulfonamides
• Tetrahydroisoquinolines
• H 85
• Becaplermin
• Colforsin
• 8-Bromo Cyclic Adenosine Monophosphate
• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C
• Calcium-Calmodulin-Dependent Protein Kinases
• Phospholipase D
• Adenylyl Cyclases
• calphostin C
• zelandopam
• N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
• Dopamine

Topics

• 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (pharmacology)
• 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
• Adenylyl Cyclases (metabolism)
• Animals
• Becaplermin
• Calcium-Calmodulin-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Cell Division (drug effects)
• Cell Movement (drug effects)
• Cells, Cultured
• Colforsin (pharmacology)
• Cyclic AMP (physiology)
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors)
• Dopamine (pharmacology)
• Dopamine Agonists (pharmacology)
• Dopamine Antagonists (pharmacology)
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• Growth Inhibitors (pharmacology)
• Isoquinolines (pharmacology)
• Muscle, Smooth, Vascular (cytology, drug effects)
• Naphthalenes (pharmacology)
• Phospholipase D (antagonists & inhibitors, metabolism)
• Platelet-Derived Growth Factor (pharmacology)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-sis
• Rats
• Rats, Wistar
• Receptors, Dopamine D1 (drug effects, physiology)
• Renal Artery (cytology)
• Signal Transduction (drug effects, physiology)
• Sulfonamides
• Tetrahydroisoquinolines