Urocortin decreases phosphorylation of MYPT1 and increases the myosin phosphatase activity via elevation of the intracellular level of cAMP

• Published in: Biofizika Vol. 51; no. 5; p. 773
• Main Authors: Lubomirov, L T, Schubert, R, Gagov, H S, Duridanova, D B, Pfitzer, G
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01.09.2006
• Subjects: Animals; Arteries - physiology; Calcium - physiology; Corticotropin-Releasing Hormone - physiology; Cyclic AMP - metabolism; In Vitro Techniques; Intracellular Space - metabolism; Mice; Muscle, Smooth, Vascular - physiology; Myosin-Light-Chain Kinase - metabolism; Myosin-Light-Chain Phosphatase - metabolism; Phosphorylation; Receptors, Corticotropin-Releasing Hormone - agonists; Tail - blood supply; Urocortins; Vasodilation
• ISSN: 0006-3029

Urocortin, a peptide hormone related to the corticotropin releasing factor, is suggested to be involved in blood pressure regulation by dilating the peripheral blood vessels. In rat tail arteries, urocortin-induced vasodilation is due to a decrease in myofilament Ca2+ sensitivity the mechanism of which is still unclear. In this study, the hypothesis was tested that the decrease in Ca2+ sensitivity in mouse tail arteries results from the activation of myosin light chain phosphatase. The relaxation of KCl-precontracted (42 mM) intact mouse tail arteries by urocortin (1 nM and 10 nM) was significantly inhibited by 1 microM antisauvagine30, a CRF-2 receptor antagonist (p < 0.05, n = 3). The addition of 1 microM KT 5720, an inhibitor of PKA, to intact rat tail arteries did not affect the KCl-induced force but significantly attenuated the urocortin-induced relaxation (n = 5). In alpha-toxin permeabilized mouse tail arteries, urocortin relaxed submaximally activated preparations at constant pCa 6.1 by 37.6 +/- 8.2% (n = 5) as compared to control vessels (n = 5, p < 0.001). The relaxation in permeabilized vessels was inhibited by pre-treatment with 30 microM Rp-8-CPT-cAMPS, an inactive analogue of cAMP. In permeabilized mouse tail arteries, treatment with 100 nM urocortin was associated with dephosphorylation of MLC20(Ser19) and MYPT1(Thr696/Thr850). The effect of urocortin on MYPTI dephosphorylation was completely abolished by 30 M Rp-8-CPT-cAMPS and mimicked by the cAMP analogue Sp-5,6-DCI-cBiMPS. Based on these findings, we propose that the urocortin-induced relaxation is due to a decrease in calcium sensitivity mediated by a cAMP-dependent increase in the activity of MLCP.