Urocortin-Induced Decrease in Ca 2+ Sensitivity of Contraction in Mouse Tail Arteries Is Attributable to cAMP-Dependent Dephosphorylation of MYPT1 and Activation of Myosin Light Chain Phosphatase (original) (raw)

Urocortin, a vasodilatory peptide related to corticotropin-releasing factor, may be an endogenous regulator of blood pressure. In vitro, rat tail arteries are relaxed by urocortin by a cAMP-mediated decrease in myofilament Ca 2+ sensitivity through a still unclear mechanism. Here we show that contraction of intact mouse tail arteries induced with 42 mmol/L KCl or 0.5 μmol/L noradrenaline was associated with a ≈2-fold increase in the phosphorylation of the regulatory subunit of myosin phosphatase (SMPP-1M), MYPT1, at Thr696, which was reversed in arteries relaxed with urocortin. Submaximally (pCa 6.1) contracted mouse tail arteries permeabilized with α-toxin were relaxed with urocortin by 39±3% at constant [Ca 2+ ], which was associated with a decrease in myosin light chain (MLC 20 Ser19 ), MYPT1 Thr696 , and MYPT1 Thr850 phosphorylation by 60%, 28%, and 52%, respectively. The Rho-associated kinase (ROK) inhibitor Y-27632 decreased MYPT1 phosphorylation by a similar extent. Inhibitio...