Pharmacologic inhibition of the renal outer medullary potassium channel causes diuresis and natriuresis in the absence of kaliuresiss

Journal of Pharmacology and Experimental Therapeutics

Volumn 348, Issue 1, 2014, Pages 153-164

  Garcia, Maria L ^a   Priest, Birgit T ^a   Alonso Galicia, Magdalena ^b   Zhou, Xiaoyan ^b   Felix, John P ^a   Brochu, Richard M ^a   Bailey, Timothy ^a   Thomas Fowlkes, Brande ^a   Liu, Jessica ^a   Swensen, Andrew ^a   Pai, Lee Yuh ^b   Xiao, Jianying ^b   Hernandez, Melba ^b   Hoagland, Kimberly ^a   Owens, Karen ^c   Tang, Haifeng ^d   De Jesus, Reynalda K ^d   Roy, Sophie ^b   Kaczorowski, Gregory J ^a   Pasternak, Alexander ^d  

^a Departments of Ion Channels   (United States)

^b Hypertension ^*  (United States)

^c Biomolecular Screening   (United States)

^d Merck Discovery Chemistry   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 [2 [4 [2 [4 (1H TETRAZOL 1 YL)PHENYL]ACETYL]PIPERAZIN 1 YL]ETHETHYL]; DIURETIC AGENT; HYDROCHLOROTHIAZIDE; POTASSIUM; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL KIR1.1; RENAL OUTER MEDULLARY POTASSIUM CHANNEL; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BARTTER SYNDROME; BLOOD PRESSURE REGULATION; CONTINUOUS INFUSION; CONTROLLED STUDY; CYTOPLASM; DIURESIS; DOSE RESPONSE; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; GENE MUTATION; HETEROZYGOTE; HUMAN; HUMAN CELL; HYPERTENSION; HYPOKALEMIA; IN VIVO STUDY; KALIURESIS; MALE; MEMBRANE BINDING; MOUSE; NATRIURESIS; NONHUMAN; PLASMA CLEARANCE; POTASSIUM BLOOD LEVEL; POTASSIUM EXCRETION; PRIORITY JOURNAL; RAT; RISK REDUCTION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; DIURESIS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEK293 CELLS; HUMANS; MADIN DARBY CANINE KIDNEY CELLS; MALE; NATRIURESIS; POTASSIUM CHANNEL BLOCKERS; POTASSIUM CHANNELS, INWARDLY RECTIFYING; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84889825613     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.113.208603     Document Type: Article

References (26)

1. Abbadie C, McManus OB, Sun SY, Bugianesi RM, Dai G, Haedo RJ, Herrington JB, Kaczorowski GJ, Smith MM, and Swensen AM, et al. (2010) Analgesic effects of a substituted N-triazole oxindole (TROX-1), a state-dependent, voltage-gated calcium channel 2 blocker. J Pharmacol Exp Ther 334:545-555.
2. Bhave G, Chauder BA, Liu W, Dawson ES, Kadakia R, Nguyen TT, Lewis LM, Meiler J, Weaver CD, and Satlin LM, et al. (2011) Development of a selective smallmolecule inhibitor of Kir1.1, the renal outer medullary potassium channel. Mol Pharmacol 79:42-50.
3. Felix JP, Liu J, Schmalhofer WA, Bailey T, Bednarek MA, Kinkel S, Weinglass AB, Kohler M, Kaczorowski GJ, and Priest BT, et al. (2006) Characterization of Kir1.1 channels with the use of a radiolabeled derivative of tertiapin. Biochemistry 45: 10129-10139.
4. Felix JP, Priest BT, Solly K, Bailey T, Brochu RM, Liu CJ, Kohler MG, Kiss L, Alonso-Galicia M, and Tang H, et al. (2012) The inwardly rectifying potassium channel Kir1.1: development of functional assays to identify and characterize channel inhibitors. Assay Drug Dev Technol 10:417-431.
5. Felix JP, Williams BS, Priest BT, Brochu RM, Dick IE, Warren VA, Yan L, Slaughter RS, Kaczorowski GJ, and Smith MM, et al. (2004) Functional assay of voltagegated sodium channels using membrane potential-sensitive dyes. Assay Drug Dev Technol 2:260-268.
6. Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, and Lifton RP (2008) Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40:592-599.
7. Jin W and Lu Z (1998) A novel high-affinity inhibitor for inward-rectifier K1 channels. Biochemistry 37:13291-13299.
8. Lewis LM, Bhave G, Chauder BA, Banerjee S, Lornsen KA, Redha R, Fallen K, Lindsley CW, Weaver CD, and Denton JS (2009) High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1. Mol Pharmacol 76:1094-1103.
9. Lifton RP, Gharavi AG, and Geller DS (2001) Molecular mechanisms of human hypertension. Cell 104:545-556.
10. Lorenz JN, Baird NR, Judd LM, Noonan WT, Andringa A, Doetschman T, Manning PA, Liu LH, Miller ML, and Shull GE (2002) Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter's syndrome. J Biol Chem 277:37871-37880.
11. Lu M, Wang T, Yan Q, Yang X, Dong K, Knepper MA, Wang W, Giebisch G, Shull GE, and Hebert SC (2002) Absence of small conductance K1 channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice. J Biol Chem 277:37881-37887.
12. Lu Z and MacKinnon R (1994) Electrostatic tuning of Mg21 affinity in an inwardrectifier K1 channel. Nature 371:243-246.
13. Nichols CG and Lopatin AN (1997) Inward rectifier potassium channels. Annu Rev Physiol 59:171-191.
14. Palmer BF and Naderi AS (2007) Metabolic complications associated with use of thiazide diuretics. J Am Soc Hypertens 1:381-392.
15. Palmer LG, Choe H, and Frindt G (1997) Is the secretory K channel in the rat CCT ROMK? Am J Physiol 273:F404-F410.
16. Rieg T, Vallon V, Sausbier M, Sausbier U, Kaissling B, Ruth P, and Osswald H (2007) The role of the BK channel in potassium homeostasis and flow-induced renal potassium excretion. Kidney Int 72:566-573.
17. Schmalhofer WA, Swensen AM, Thomas BS, Felix JP, Haedo RJ, Solly K, Kiss L, Kaczorowski GJ, and Garcia ML (2010) A pharmacologically validated, highcapacity, functional thallium flux assay for the human Ether-à-go-go related gene potassium channel. Assay Drug Dev Technol 8:714-726.
18. Simon DB, Karet FE, Rodriguez-Soriano J, Hamdan JH, DiPietro A, Trachtman H, Sanjad SA, and Lifton RP (1996) Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K1 channel, ROMK. Nat Genet 14:152-156.
19. Simons K and Virta H (2006) Growing Madin-Darby canine kidney cells for studying epithelial cell biology, in Cell Biology (Celis JE, ed) pp 127-131, Elsevier, New York.
20. Solly K, Cassaday J, Felix JP, Garcia ML, Ferrer M, Strulovici B, and Kiss L (2008) Miniaturization and HTS of a FRET-based membrane potential assay for K(ir) channel inhibitors. Assay Drug Dev Technol 6:225-234.
21. Sood N, Reinhart KM, and Baker WL (2010) Combination therapy for the management of hypertension: A review of the evidence. Am J Health Syst Pharm 67: 885-894.
22. Tang H, Walsh SP, Yan Y, de Jesus RK, Shahripour A, Teumelsan N, Zhu Y, Ha S, Owens KA, and Thomas-Fowlkes B, et al. (2012) Discovery of selective small molecule ROMK inhibitors as potential new mechanism diuretics. ACS Med Chem Lett 3:367-372 DOI: 10.1021/ml3000066.
23. Tang H, de Jesus RK, Walsh SP, Zhu Y, Yan Y, Priest BT, Swensen AM, Alonso-Galicia M, Felix JP, and Brochu RM, et al. (2013) Discovery of a novel sub-class of ROMK channel inhibitors typified by 5-(2-(4-(2-(4-(1H-Tetrazol-1- yl)phenyl) acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one. Bioorg Med Chem Lett 23:5829-5832.
24. Tao X, Avalos JL, Chen J, and MacKinnon R (2009) Crystal structure of the eukaryotic strong inward-rectifier K1 channel Kir2.2 at 3.1 Å resolution. Science 326:1668-1674.
25. Xu JZ, Hall AE, Peterson LN, Bienkowski MJ, Eessalu TE, and Hebert SC (1997) Localization of the ROMK protein on apical membranes of rat kidney nephron segments. Am J Physiol 273:F739-F748.
26. Zhou X, Zhang Z, Shin MK, Horwitz SB, Levorse JM, Zhu L, Sharif-Rodriguez W, Streltsov DY, Dajee M, and Hernandez M, et al. (2013) Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure. Hypertension 62:288-294.