a2-Adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells

Richman, Jeremy G., and John W. Regan. a2-Adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells. Am. J. Physiol. 274 (Cell Physiol. 43): C654–C662, 1998.—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 a2-adrenergic receptors (a2-ARs) might have in these cellular responses, we characterized the a2-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 a2-AR subtypes (a2A, a2B, and a2C) were initially present. Mitogenactivated protein kinase activity in the RASM cells was stimulated fivefold over basal by the a2-selective agonist dexmedetomidine (Dex) and was blocked by coincubation with the a2-selective antagonist rauwolscine (RW) or by preincubation of the cells with the Gi/Go-protein inhibitor pertussis toxin. a2-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 a2-ARs in RASM cells. The involvement of a2-AR activation with cytoskeletal changes and cell migration is novel and indicates a potential role of these receptors in vascular wound healing and pathogenesis.