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β1‐Adrenergic receptor signaling activates TRPV5 via the protein kinase A pathway (1181.4)
Author(s) -
Hoenderop Joost,
Hagen Eline,
Tudpor Kukiat,
Verkaart Sjoerd,
Bindels Rene
Publication year - 2014
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.28.1_supplement.1181.4
Subject(s) - reabsorption , chemistry , receptor , endocrinology , medicine , hek 293 cells , agonist , protein kinase a , microbiology and biotechnology , phosphorylation , kidney , biology , biochemistry
Epinephrine (Epi) and norepinephrine (NE) are present in the pro‐urine. Active Ca2+ reabsorption in the late distal convoluted and connecting tubules (DCT2/CNT) is initiated by Ca2+ influx through the transient receptor potential vanilloid type 5 (TRPV5) Ca2+ channel. Although it was reported that β‐adrenergic receptors (β‐AR) are present in the DCT2/CNT region, their role in active Ca2+ reabsorption remains elusive. Here we revealed that β1‐AR, but not β2‐AR is colocalized with TRPV5 in DCT2/CNT. Subsequently, treatment of TRPV5‐expressing mouse DCT2/CNT primary cell cultures with the β1‐AR agonist dobutamine showed enhanced apical‐to‐basolateral transepithelial Ca2+ reabsorption. In human embryonic kidney (HEK293) cells, dobutamine was shown to stimulate cAMP production, signifying functional β1‐AR‐expression. Fura‐2 experiments demonstrated increased activity of the TRPV5 Ca2+ channel with dobutamine, which could be prevented by the PKA inhibitor H89. Moreover, non‐phosphorylable T709A‐TRPV5 and phosphorylation‐mimicking T709D‐TRPV5 mutants are unresponsive to dobutamine. Surface biotinylation showed that dobutamine did not affect plasma membrane abundance of TRPV5. In conclusion, activation of β1‐AR stimulates active Ca2+ reabsorption in DCT2/CNT, increase in TRPV5 activity via PKA phosphorylation of residue T709 possibly plays an important role.