Regulation of human vascular smooth muscle cell migration by beta-adrenergic receptors.
Migration and proliferation of vascular smooth muscle cells (VSMCs) are two events involved in atherosclerosis, restenosis after balloon angioplasty, and stenosis of grafted vessels. Platelet-derived growth factor (PDGF) found in stenotic vessels is known to induce migration of VSMCs. VSMCs express both alpha- and beta-adrenergic receptors on their surface, and blood vessels are innervated by the adrenergic nervous system and exposed to circulating epinephrine. We examined the role of these receptors on PDGF-induced migration of VSMCs. VSMCs were cultured from saphenous vein segments. Migration was stimulated by PDGF. Effect of pretreatment of VSMCs with the beta-agonist isoproterenol, the alpha-agonist phenylephrine, or forskolin on PDGF-induced migration was examined with a modified Boyden chamber. Cell migration was quantitated by spectrophotometry. Intracellular cyclic AMP was determined by radioimmunoassay. PDGF significantly induced VSMC migration. Isoproterenol (0.1 and 1.0 microM) inhibited PDGF-induced migration by 30 per cent and 50 per cent, respectively. Forskolin (10 microM) completely blocked PDGF-induced migration. The migration inhibition by isoproterenol or forskolin was associated with a significant elevation of intracellular cyclic AMP. In contrast, phenylephrine had no effect on PDGF-induced migration or on cyclic AMP. Activation of beta-adrenergic receptors and the consequent rise in intracellular cyclic AMP inhibits migration of VSMCs induced by PDGF. These results are consistent with the notion that adrenergic agonists with substantial beta-receptor affinity, such as isoproterenol, can inhibit smooth muscle cell migration.
Department of Surgery, Mercer University School of Medicine, Macon, Georgia 31207, USA.
Richard
R
Johnson
Jerry G
JG
Webb
Walter H
WH
Newman
Zhongbiao
Z
Wang
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology; D013053:Spectrophotometry
D000318:Adrenergic beta-Agonists; D010982:Platelet-Derived Growth Factor; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D010656:Phenylephrine; D000242:Cyclic AMP; D007545:Isoproterenol