distinct effects of contraction agonists on the phosphorylation state of cofilin in pulmonary artery smooth muscle不同的收缩受体激动剂对cofilin的磷酸化状态的影响在肺动脉平滑肌.pdfVIP

Hindawi Publishing Corporation Advances in Pharmacological Sciences Volume 2008, Article ID 362741, 9 pages doi:10.1155/2008/362741 Research Article Distinct Effects of Contraction Agonists on the Phosphorylation State of Cofilin in Pulmonary Artery Smooth Muscle Yan-Ping Dai,1 Shaner Bongalon,1 Violeta N. Mutafova-Yambolieva,2 and Ilia A. Yamboliev1 1 Department of Pharmacology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557, USA 2 Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA Correspondence should be addressed to Ilia A. Yamboliev, iyamboliev@ Received 5 March 2007; Accepted 24 July 2007 Recommended by Charles Klodell We hypothesized that agonist-induced contraction correlates with the phosphocofilin/cofilin (P-CF/CF) ratio in pulmonary artery (PA) rings and cultured smooth muscle cells (PASMCs). PA rings were used for isometric contractions and along with PASMCs for assay of P-CF/CF by isoelectric focusing and immunoblotting. The P-CF/CF measured 22.5% in PA and differentiated PASMCs, but only 14.8% in undifferentiated PASMCs. With comparable contraction responses in PA, endothelin-1 (100 nM) and nore- pinephrine (1 μM) induced a 2-fold increase of P-CF/CF, while angiotensin II (1 μM) induced none. All agonists activated Rho- kinase and LIMK2, and activation was eliminated by inhibition of Rho-kinase. Microcystin LF (20 nM) potentiated the angiotensin II, but not the 5-hydroxytryptamine (1 μM)-mediated increase of P-CF/CF. In conclusion, all tested agonists activate the Rho- kinase-LIMK pathway and increase P-CF/CF. Angiotensin II activates PP2A and counteracts the LIMK-mediated CF phosphory- lation. CF phosphorylation stabilizes peripheral actin structures and may contribut