Tags

Type your tag names separated by a space and hit enter

Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase.
J Am Soc Nephrol. 2006 Sep; 17(9):2457-63.JA

Abstract

Initiation of tubuloglomerular feedback (TGF) depends on Na-K-2Cl co-transport in the macula densa (MD), but it is less clear whether Na,K-ATPase is responsible for establishing the inward Na+ gradient. It has been proposed that apical colonic H,K-ATPase, perhaps in concert with the Na/H exchanger (NHE2), may account for MD Na+ exit in these cells. This study evaluated TGF responses by micropuncture in mutant mice with altered ouabain sensitivity of the alpha1 and alpha2 Na,K-ATPase isoforms. TGF responses in alpha1-sensitive/alpha2-resistant mice were inhibited by intravenous ouabain (control stop-flow pressure = 9.7 +/- 0.9 versus 1.6 +/- 0.5 mmHg with intravenous ouabain). Subsequent inclusion of cyclohexyladenosine (10 microM) in the tubule perfusate confirmed the ability of the afferent arteriole to contract in the presence of ouabain. In alpha1-resistant/alpha2-resistant mice, ouabain infusion had no effect on TGF responses. In separate experiments, loop of Henle perfusion with 50 microM ouabain decreased TGF responses (control stop-flow pressure) from 10.5 +/- 1.1 to 3.9 +/- 1.0 mmHg in alpha1-sensitive/alpha2-resistant mice but had no effect in alpha1-resistant/alpha2-resistant mice, and afferent arteriole responsiveness again was confirmed by cyclohexyladenosine. TGF responses in NHE2 and colonic H,K-ATPase knockout mice were not different from those of wild-type mice. These data indicate that TGF requires activity of the alpha1 Na,K-ATPase, presumably in the MD. Furthermore, the data show that neither NHE2 nor colonic H,K-ATPase is essential for initiation of TGF responses.

Authors+Show Affiliations

Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0576, USA. john.lorenz@ucmail.uc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16870707

Citation

Lorenz, John N., et al. "Ouabain Inhibits Tubuloglomerular Feedback in Mutant Mice With Ouabain-sensitive Alpha1 Na,K-ATPase." Journal of the American Society of Nephrology : JASN, vol. 17, no. 9, 2006, pp. 2457-63.
Lorenz JN, Dostanic-Larson I, Shull GE, et al. Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase. J Am Soc Nephrol. 2006;17(9):2457-63.
Lorenz, J. N., Dostanic-Larson, I., Shull, G. E., & Lingrel, J. B. (2006). Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase. Journal of the American Society of Nephrology : JASN, 17(9), 2457-63.
Lorenz JN, et al. Ouabain Inhibits Tubuloglomerular Feedback in Mutant Mice With Ouabain-sensitive Alpha1 Na,K-ATPase. J Am Soc Nephrol. 2006;17(9):2457-63. PubMed PMID: 16870707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na,K-ATPase. AU - Lorenz,John N, AU - Dostanic-Larson,Iva, AU - Shull,Gary E, AU - Lingrel,Jerry B, Y1 - 2006/07/26/ PY - 2006/7/28/pubmed PY - 2006/12/23/medline PY - 2006/7/28/entrez SP - 2457 EP - 63 JF - Journal of the American Society of Nephrology : JASN JO - J Am Soc Nephrol VL - 17 IS - 9 N2 - Initiation of tubuloglomerular feedback (TGF) depends on Na-K-2Cl co-transport in the macula densa (MD), but it is less clear whether Na,K-ATPase is responsible for establishing the inward Na+ gradient. It has been proposed that apical colonic H,K-ATPase, perhaps in concert with the Na/H exchanger (NHE2), may account for MD Na+ exit in these cells. This study evaluated TGF responses by micropuncture in mutant mice with altered ouabain sensitivity of the alpha1 and alpha2 Na,K-ATPase isoforms. TGF responses in alpha1-sensitive/alpha2-resistant mice were inhibited by intravenous ouabain (control stop-flow pressure = 9.7 +/- 0.9 versus 1.6 +/- 0.5 mmHg with intravenous ouabain). Subsequent inclusion of cyclohexyladenosine (10 microM) in the tubule perfusate confirmed the ability of the afferent arteriole to contract in the presence of ouabain. In alpha1-resistant/alpha2-resistant mice, ouabain infusion had no effect on TGF responses. In separate experiments, loop of Henle perfusion with 50 microM ouabain decreased TGF responses (control stop-flow pressure) from 10.5 +/- 1.1 to 3.9 +/- 1.0 mmHg in alpha1-sensitive/alpha2-resistant mice but had no effect in alpha1-resistant/alpha2-resistant mice, and afferent arteriole responsiveness again was confirmed by cyclohexyladenosine. TGF responses in NHE2 and colonic H,K-ATPase knockout mice were not different from those of wild-type mice. These data indicate that TGF requires activity of the alpha1 Na,K-ATPase, presumably in the MD. Furthermore, the data show that neither NHE2 nor colonic H,K-ATPase is essential for initiation of TGF responses. SN - 1046-6673 UR - https://www.unboundmedicine.com/medline/citation/16870707/Ouabain_inhibits_tubuloglomerular_feedback_in_mutant_mice_with_ouabain_sensitive_alpha1_NaK_ATPase_ L2 - https://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=16870707 DB - PRIME DP - Unbound Medicine ER -