title: Distinct effects of contraction agonists on the phosphorylation state of cofilin in pulmonary artery smooth muscle.
abstract: We hypothesized that agonist-induced contraction correlates with the phospho-cofilin/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 norepinephrine (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 phosphorylation. CF phosphorylation stabilizes peripheral actin structures and may contribute to the maximal contraction of PA.
authors.affiliation: Department of Pharmacology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Dai
authors.forename: Shaner
authors.initials: S
authors.lastname: Bongalon
authors.forename: Violeta N
authors.initials: VN
authors.lastname: Mutafova-Yambolieva
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Yamboliev