Alpha 2-adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells.
Vascular wound healing and such pathologies as atherosclerosis and restenosis are characterized by migration and proliferation of the smooth muscle cells of the media after denudation of the intima. To explore possible roles that alpha 2-adrenergic receptors (alpha 2-ARs) might have in these cellular responses, we characterized the alpha 2-ARs present in explant-derived cultures of rat aortic smooth muscle (RASM) cells. The results of immunofluorescence microscopy and reverse transcription followed by the polymerase chain reaction indicated that all three alpha 2-AR subtypes (alpha 2A, alpha 2B, and alpha 2C) were initially present. Mitogen-activated protein kinase activity in the RASM cells was stimulated fivefold over basal by the alpha 2-selective agonist dexmedetomidine (Dex) and was blocked by coincubation with the alpha 2-selective antagonist rauwolscine (RW) or by preincubation of the cells with the Gi/G(o)-protein inhibitor pertussis toxin. alpha 2-AR activation by Dex did not promote cell proliferation, as measured by the incorporation of [3H]thymidine. However, Dex significantly increased RASM cell migration, and antagonist blocked this effect. Incubation of RASM cells with Dex also produced a marked decrease in F-actin labeling, which again was prevented by coincubation with RW. The evidence clearly reveals the presence of functional alpha 2-ARs in RASM cells. The involvement of alpha 2-AR activation with cytoskeletal changes and cell migration is novel and indicates a potential role of these receptors in vascular wound healing and pathogenesis.
Richman
J G
JG
Department of Pharmacology and Toxicology, University of Arizona, Tucson 85721-0207, USA.
Regan
J W
JW
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
D000199:Actins; D005938:Glucocorticoids; D018341:Receptors, Adrenergic, alpha-2; D003907:Dexamethasone; D017871:Calcium-Calmodulin-Dependent Protein Kinases