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| 〖删除〗〖版主编辑〗〖转移帖子〗〖顶〗〖精〗[回复][短消息][编辑] | | 一氧化氮在心脏中的活动 | Nitric oxide (NO) has a number of important physiological actions in the cardiovascular system. In the heart, NO plays role in keeping the vessels patent via vasodilation and prevention of platelet aggregation. It also plays an important role in regulating the force and rate of contraction. In vivo NO is released by shear stress of ligands that increase intracellular Ca2+ in endothelial cells. The increase intracellular Ca2+ activates nitric oxide synthase III (NOSIII) by promoting the binding of Ca/Calmodulin to the enzyme. NOSIII, which is resident in the Golgi complex, is transported together with caveolin-1 to the caveolae at the plasma membrane via vesicles. Shear stress signals via a potassium channel and the cytoskeleton, which results in tyrosine phosphorylation of specific proteins, activation of phosphatidylinositol 3-kinase, and subsequently in activation of Akt kinase. Akt activation by shear stress but also by VEGF activates NOSIII by serine phosphorylation, which increases the affinity of NOSIII for calmodulin. After agonist binding at the plasma membrane, NOSIII-activating receptors translocate to caveolae. VEGF receptor signals via its tyrosine kinase domain. Furthermore, agonist receptors activate calcium channels of the endoplasmic reticulum (ER) via phospholipase C and inositol 1,4,5-trisphosphate. This calcium flux induces binding of calmodulin to NOSIII, whereas the NOSIII-caveolin-1 interaction is disrupted. At the same time, NOSIII is translocated into the cytosol. On binding of calmodulin, NOSIII generates NO, is enhanced by the interaction with Hsp90. Once activated, NOSIII catabolizes L-arginine to NO, which diffuses out of the cell. NO stimulates guanylate (G-) cyclase and increases cGMP levels. cGMP activates cGMP-dependent protein kinase (PKG), cGMP-inhibited phosphodiesterase (PDEIII), and cGMP-stimulated phosphodiesterase (PDEII). PKG may reduce the force and rate of contraction, possibly by phosphorylating troponin I or by phosphorylating phospholamban. PDEIII is inhibited by the increases in cGMP brought about by NO. This may result in an increase in cAMP and cAMP-dependent protein kinase (PKA). PKA in turn activates Ca2+ channels, countering the effects of PKG. In contrast, cGMP may stimulate PDEII, reduce cAMP levels and PKA activity, and thereby reduce Ca2+ channel activity. Ach, acetylcholine. CAT-1, cationic amino acid transporter.
Kosi Gramatikoff, PhD
Alderton WK, Cooper CE, and Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J., vol 357(Pt 3), March 2001, 593-615. Review.
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Kaumann, Alberto, et al. Activation of b2-Adrenergic Receptors Hastens Relaxation and Mediates Phosphorylation of Phospholamban, Troponin I, and C-Protein in Ventricular Myocardium from Patients with Terminal Heart Failure. Circulation, vol 99, 1999, 65-72.
Kelly RA, et al. Nitric oxide and cardiac function. Circ Res., Vol 79(3), September 1996, 363-80.
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Mayer, Bernd, et al. A New Pathway of Nitric Oxide/Cyclic GMP Signaling Involving S-Nitrosoglutathione. Biochem. J., vol 273(6), February 1998, 3264-70.
McDonald KK, Zharikov S, Block ER, and Kilberg MS. A Caveolar Complex between the Cationic Amino Acid Transporter 1 and Endothelial Nitric-oxide Synthase May Explain the Arginine Paradox. Biochem. J., vol 272(50), December 1997, 31213-16.
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| 最初发表时间：2006-5-1 |  | | 昔者庄周梦为蝴蝶，栩栩然蝴蝶也。自喻适志与！不知周也。俄然觉，则蘧蘧然周也。不知周之梦为蝴蝶与，蝴蝶之梦为周与？周与蝴蝶，则必有分矣。此之谓物化。 |
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