Stimulation of DNA synthesis, activation of mitogen-activated protein kinase ERK2 and nuclear accumulation of c-fos in human aortic smooth muscle cells by ketamine

• Published in: Cell proliferation 2002-06, Vol.35 (3), p.155-165
• Main Authors: Boulom, V., Lee, H.-W., Zhao, L., Eghbali-Webb, M.
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; Anesthetics, Dissociative - pharmacology; Aorta - cytology; Cell Line; Cell Nucleus - metabolism; DNA - biosynthesis; Enzyme Activation; Female; Humans; Infant; Ketamine - pharmacology; Mitogen-Activated Protein Kinase 1 - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Original; Proto-Oncogene Proteins c-fos - metabolism
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1046/j.1365-2184.2002.00233.x

. Proliferation of vascular smooth muscle cells is known to be regulated by autocrine and paracrine stimuli, including extracellular matrix, reactive oxygen species, lipids, and biomechanical forces. The effect of many pharmacological agents to which smooth muscle cells may be exposed, however, is widely unexplored. Ketamine, an intravenous anaesthetic and a phencyclidine derivative, regulates diverse intracellular signalling pathways in smooth muscle cells, several of which are known to affect cell proliferation. The effect of ketamine on proliferative response of smooth muscle cells, however, is not determined. We tested the hypothesis that ketamine may regulate proliferation of smooth muscle cells, and investigated the effects of pharmacological doses of ketamine on their proliferative capacity by measuring DNA synthesis and activation of mitogen‐activated protein (MAP) kinase signalling pathway in human aortic smooth muscle cells. DNA synthesis, as determined by incorporation of 3H‐thymidine into DNA, was enhanced by 73% (P