K+ATP channels

Liss B, Haeckel O, Wildmann J et al (2005) K-ATP channels promote tire differential degeneration of dopaminergic midbrain neurons. Nat Neurosci 8 1742-1751... 

Kir6.2/SUR1 K ATP channels ZINC db (65 K), FLAP screening to 1,913 compounds 3 hits of 32 tested [66, 67]... 

Nelson There are also studies indicating that the K ATP channel openers are useful in certain types of incontinence. This is also working on the bladder smooth muscle. 

Brading K+-ATP channels are marvellous they stop all of the unstable contractions in the bladder straight off. The only problem is that they do everything else as well. 

Stefani MR, Gold PE. 2001. Intrahippocampal infusions of K-ATP channel modulators influence spontaneous alternation performance Relationship to acetylcholine release in the hippocapus. The Journal of Neuroscience 21(2) 609-614. 

Ashcroft SJ. The beta-cell K(ATP) channel. J Membr Biol 2001 176 187-206. 

Hanley PJ, Daut J. (2005) K(ATP) channels and preconditioning A re-examination of the role of mitochondrial K(ATP) charmels and an overview of alternative mechanisms. J Mol Cell Cardiol 59, 17-50. 

Thomzig, A., Wenzel, M., Karschin, C., Eaton, M. J., Skatchkov, S. N., Karschin, A., Veh, R. W. Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels, Molecular and Cellular Neuroscience 2001, 18, 671-690. 

Tomai F, Danesi A, Ghini AS, Crea F, Perino M, Gaspardone A, Ruggeri G, Chiariello L, Gioffre PA. Effects of K(ATP) channel blockade by glibenclamide... 

Bryan J, Crane A, Vila-Carriles WH, et al. Insulin sec-retagogues, sulfonylurea receptors and K(ATP) channels. Curr Pharm Des. 2005 11 2699-2716. 

The Blockade of K+-ATP Channels has Neuro-protective Effects in an In Vitro Model of Brain Ischemia... 

Our iterative ion channel library design process is outlined in Figure 8.13. Retrieval and critical review of literature and in-house data on ion channel modulators resulted in a collection of valuable lead compounds, suitable for 2D and 3D database mining in internal and external compound collections. Among others, we took into account calcium channel blockers like Clonidine, chloride channel blockers, potassium channel openers, K(ATP) channel blocker and openers (e.g., Glibenclamide), and NHE-1 inhibitors. 

Uhrig U, Holtje HD, Mannhold R, Weber H, Lemoine H. Molecular modeling and QSAR studies on K(ATP) channel openers of the benzopyran type. J Mol Graph Model 2002 21 37-45. 

D.A. Mei, K. Nithipatikom, R.D. Lasley and G.J. Gross, Myocardial preconditioning produced by ischemia, hypoxia and a K(ATP) channel opener effects on intestitial adenosine in dogs, J. Mol. Cell. Cardiol. 30, 1225-1236 (1998). 

C.H. Tsai, S.F. Su, T.F. Chou and T.M. Lee, Differential effects of sarcolemmal and mitochondrial K(ATP) channels activated by 17 beta estradiol on repcrfusion arrhythmias and infarct sizes in canine hearts, J. Pharmacol. Exp. Ther. 301, 234-240 (2002). 

Hypothalamic proopiomelanocortin neurons are glucose responsive and express K(ATP) channels. Endocrinology 144 1331-1340. 

Roeper J, Ashcroft FM. 2002. Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones. Pfiugers Arch 405 305-309. 

Ann Sulin is taking a sulfonylurea compound known as glipizide to treat her diabetes. The sulfony-lureas act on the K atp channels on the surface of the pancreatic (5 cells. The binding of the drug to these channels closes K+ channels (as do elevated ATP levels), which, in turn, increases Ca + movement into the interior of the p cell. This influx of calcium modulates the interaction of the insulin storage vesicles with the plasma membrane of the p cell, resulting in the release of insulin into the circulation. 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

Eicosapentaenoic acid (EPA, 20 5n-3), docosahexaenoic acid (DHA, 22 6n-3) (Figure 4), and a-linolenic acid (ALA, 18 3n-3, rich in plant oils) are three major -3 essential fatty aeids involved in eardiovascular function and general circulation. Administration of EPA can 1) induce endothelium-independent aortic and mesenteric vasodilation via activation of K atp channels on VSMCs via EPA-derived prostanoids [27], 2) Activation of large-conductance/Ca -mediated channels (BK) on VSMCs by EPA metabolite, 17,18-EET [28]. 

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