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ATP mediates flow‐induced nitric oxide production in thick ascending limbs by activating luminal and basolateral P2 receptors
Author(s) -
Cabral Pablo,
Garvin Jeffrey L.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb813
Subject(s) - nitric oxide , receptor , chemistry , purinergic receptor , p2y receptor , medicine , endocrinology , biochemistry , biology
In the thick ascending limb (TAL) ATP mediates flow‐induced nitric oxide (NO) production via purinergic type 2 receptors (P2r) activation. Both P2r subtypes, P2X and P2Y, are differentially expressed in the luminal (LL) and basolateral (BL) sides of the TAL. We hypothesized that ATP mediates flow‐induced NO production in the TAL via activation of both LL and BL P2r. We measured NO production in isolated and perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nL/min stimulated NO production from 17±15 to 130±34 arbitrary units (AU)/min ( p < 0.04; n=7). The P2r antagonist suramin (300 μmol/L) reduced flow‐induced NO production by 83 ± 25 % ( p < 0.03; n = 5) when added to both LL and BL sides. Luminal hexokinase plus glucose (HK + GL) decreased flow‐induced NO production from 205.6 ± 85.6 to 36.6 ± 118.6 AU/min ( p < 0.02; n=7). Basolateral HK + GL reduced flow‐induced NO production from 186.4 ± 45.7 to 30.9 ± 38.4; p <0.005; n=6). The P2Xr selective antagonist NF023 (200 umol/L) prevented flow‐induced NO production when added to the BL side (from 286.1 ± 8.1 to −23.5 ± 17.3; p <0.01; n=6). Luminal NF023 did not affect flow‐induced NO production. We conclude that ATP mediates flow‐induced NO production in the TAL likely via activation of P2Yr at the LL and P2Xr at the BL side.