{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:12:35Z","timestamp":1718651555648},"reference-count":43,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:p>Nitric oxide (NO) exerts direct effects on nephron transport. We determined the effect of NO on Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport in a cell line (MMDD1) with properties of macula densa. Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport was measured as bumetanide-sensitive<jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup>uptake in the presence of ouabain. MMDD1 cells expressed mRNA for the neuronal isoform of nitric oxide synthase, as well as NKCC1 and NKCC2(B) isoforms of the Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransporter. Preincubation of cells with the NO donors sodium nitroprusside (SNP) or S-nitroso- N-acetylpenicillamine (SNAP) caused concentration-dependent inhibition of Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport. Both apical and basolateral Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport was inhibited by NO donors. SNP or SNAP had no significant effect on cellular levels of cGMP, cAMP, cytosolic calcium, or phosphorylation of ERK1 and ERK2. In contrast, the inhibitors of cytochrome P-450, 1-aminobenzotriazole (ABT; 10<jats:sup>\u22123<\/jats:sup>M) or ketoconazole (1.5 \u00d7 10<jats:sup>\u22125<\/jats:sup>M), completely reversed the inhibitory effect of SNAP on apical or basolateral Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport [apical: control 1.18 \u00b1 0.15 vs. SNAP (10<jats:sup>\u22124<\/jats:sup>M) 0.41 \u00b1 0.05 pmol \u00b7 mg<jats:sup>\u22121<\/jats:sup>\u00b7 5 min<jats:sup>\u22121<\/jats:sup>; P &lt; 0.001; SNAP (10<jats:sup>\u22124<\/jats:sup>M) + ABT 1.32 \u00b1 0.10 pmol \u00b7 mg<jats:sup>\u22121<\/jats:sup>\u00b7 5 min<jats:sup>\u22121<\/jats:sup>; P = not significant vs. control; n = 5]. The cytochrome P-450 epoxyeicosatrienoic acid (EET) metabolite 14,15-EET (5 \u00d7 10<jats:sup>\u22127<\/jats:sup>M) inhibited both apical and basolateral cotransport, whereas 8,9-EET and 11,12-EET had no significant effect. Although 20-hydroxyeicosatetraenoic acid inhibited apical cotransport, the inhibitor of \u03c9-hydroxylase activity HET0016 did not reverse SNAP-mediated inhibition of apical cotransport. These data indicate that NO inhibits apical and basolateral Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-2Cl<jats:sup>\u2212<\/jats:sup>cotransport in MMDD1 cells. The results suggest that the inhibitory pathway is independent of cGMP and might involve stimulation of a cytochrome P-450-dependent pathway.<\/jats:p>","DOI":"10.1152\/ajprenal.00192.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:38:08Z","timestamp":1425415088000},"page":"F1235-F1244","source":"Crossref","is-referenced-by-count":15,"title":["NO inhibits Na<sup>+<\/sup>-K<sup>+<\/sup>-2Cl<sup>\u2212<\/sup>cotransport via a cytochrome<i>P<\/i>-450-dependent pathway in renal epithelial cells (MMDD1)"],"prefix":"10.1152","volume":"284","author":[{"given":"Hao","family":"He","sequence":"first","affiliation":[{"name":"Department of Medicine, Ottawa Hospital, and the Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiina","family":"Podymow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital, and the Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Zimpelmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital, and the Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin D.","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ottawa Hospital, and the Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.6.C1383"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.29.1.320"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1989.257.3.F463"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.4.C831"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.6.F980"},{"key":"B6","doi-asserted-by":"crossref","first-page":"25677","DOI":"10.1016\/S0021-9258(18)47302-4","volume":"269","author":"Delpire E","year":"1994","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846705"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.3.679"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.3.F377"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00298-X"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1997.273.4.L807"},{"key":"B12","doi-asserted-by":"crossref","first-page":"17613","DOI":"10.1016\/S0021-9258(18)38208-5","volume":"265","author":"Homma T","year":"1990","journal-title":"J Biol Chem"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.275.4.F605"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1995.269.3.F405"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007018200"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116615"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.38.3.309"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118844"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1991.260.6.F856"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.3.F420"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17777"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.12056"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704101"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(92)90026-E"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.382"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1726"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.467"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.0075.2001"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702171"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.1999.03028.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2000.00377.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.270.1.F106"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.270.6.F919"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115653"},{"key":"B35","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1681\/ASN.V6189","volume":"6","author":"Stoos BA","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.275.2.R426"},{"key":"B37","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1681\/ASN.V1281599","volume":"12","author":"Vallon V","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.6_Pt_2.II28"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103470"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.11993"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1996.271.4.F931"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006218200"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.3.H873"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00192.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:37:45Z","timestamp":1651397865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00192.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,1]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6,1]]}},"alternative-id":["10.1152\/ajprenal.00192.2002"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00192.2002","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,1]]}}}