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PTH suppresses sodium chloride cotransporter activity by a Mapk‐dependent process
Author(s) -
Ko Benjamin,
Cooke Leslie L,
Hoover Robert S
Publication year - 2008
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.22.1_supplement.935.6
Subject(s) - diacylglycerol kinase , endocrinology , protein kinase c , mapk/erk pathway , chemistry , medicine , bisindolylmaleimide , cotransporter , stimulation , thiazide , parathyroid hormone , phospholipase c , distal convoluted tubule , sodium , signal transduction , reabsorption , biology , biochemistry , calcium , organic chemistry , blood pressure
Recently, we described that Diacylglycerol (DAG) analogues act through Ras guanyl‐releasing protein1 (RasGRP1) stimulation of ERK1/2 MAPK to decrease function and surface expression of the thiazide‐sensitive sodium chloride cotransporter (NCC). However, upstream hormonal mediators of DAG‐dependent NCC suppression have not been identified. Although PTH activates DAG through G‐protein coupled receptor activation of Phospholipase C, PTH regulation of NCC has not been demonstrated. Utilizing a mouse DCT (mDCT) cell line with native NCC activity, we investigated whether PTH may mediate suppression of NCC function through MAPK activation. Thiazide‐sensitive 22 Na + uptakes were measured by incubating mDCT cells for 15 minutes in a Cl − free medium before exposure to a 22 Na + containing medium with or without thiazide. Uptakes were determined after 15 minute incubations with vehicle, PTH (10‐7M) alone, PTH + U0126 (MEK 1/2 MAPK inhibitor), and PTH + bisindolylmaleimide (BIM, PKC inhibitor). PTH decreased NCC activity by 43.6 +/− 4.5% (p<0.05 for PTH vs. vehicle). U0126 blocked the PTH‐induced suppression while BIM had no effect on the suppression. This is consistent with our previous data that RasGRP1 and not PKC is the mediator of DAG effects on NCC activity. These studies indicate that PTH decreases NCC function via downstream activation of the MAPK pathway. This work was supported by NIH Grant K08 DK070668.