Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 Ca2+ 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 micromol/L noradrenaline was associated with a approximately 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 alpha-toxin were relaxed with urocortin by 39+/-3% at constant [Ca2+], which was associated with a decrease in myosin light chain (MLC20Ser19), MYPT1Thr696, and MYPT1Thr850 phosphorylation by 60%, 28%, and 52%, respectively. The Rho-associated kinase (ROK) inhibitor Y-27632 decreased MYPT1 phosphorylation by a similar extent. Inhibition of PP-2A with 3 nmol/L okadaic acid had no effect on MYPT1 phosphorylation, whereas inhibition of PP-1 with 3 micromol/L okadaic acid prevented dephosphorylation. Urocortin increased the rate of dephosphorylation of MLC20Ser19 approximately 2.2-fold but had no effect on the rate of contraction under conditions of, respectively, inhibited kinase and phosphatase activities. The effect of urocortin on MLC20Ser19 and MYPT1 phosphorylation was blocked by Rp-8-CPT-cAMPS and mimicked by Sp-5,6-DCl-cBIMPS. In summary, these results provide evidence that Ca(2+)-independent relaxation by urocortin can be attributed to a cAMP-mediated increased activity of SMPP-1M which at least in part is attributable to a decrease in the inhibitory phosphorylation of MYPT1.
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PMID:Urocortin-induced decrease in Ca2+ sensitivity of contraction in mouse tail arteries is attributable to cAMP-dependent dephosphorylation of MYPT1 and activation of myosin light chain phosphatase. 1657 4

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.
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PMID:[Urocortin decreases phosphorylation of MYPT1 and increases the myosin phosphatase activity via elevation of the intracellular level of cAMP]. 1713 11