Journal
FEBS JOURNAL
Volume 279, Issue 10, Pages 1857-1870Publisher
WILEY
DOI: 10.1111/j.1742-4658.2012.08566.x
Keywords
acid; calcium imaging; capsaicin; PKD1L3; PKD2L1; transient receptor potential channel
Categories
Funding
- Research and Development Program for New Bioindustry Initiatives
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20688015, 20780089]
- Japan Society for the Promotion of Science [LS037]
- Grants-in-Aid for Scientific Research [20780089, 09J04908, 22688010, 20688015, 23688016] Funding Source: KAKEN
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Polycystic kidney disease (PKD) 2L1 protein is a member of the transient receptor potential (TRP) ion channel family. In circumvallate and foliate papillae, PKD2L1 is coexpressed with PKD1L3. PKD2L1 and PKD1L3 interact through their transmembrane domain and the resulting heteromer PKD1L3/PKD2L1 owns a unique channel property called off-responses to acid stimulation, although PKD2L1 does not own this property by itself. To define the pharmacological properties of the PKD1L3/PKD2L1 channel, we developed a new method to effectively evaluate channel activity using human embryonic kidney 293T cells in which the channel was heterologously expressed. This method was applied to screen substances that potentially regulate it. We found that capsaicin and its analogs, which are TRPV1 agonists, inhibited the response to acid stimuli and that the capsaicin inhibition was reversible with an IC50 of 32.5 mu m. Capsaicin and its analogs are thus useful tools for physiological analysis of PKD1L3/PKD2L1 function. Database ?Nucleotide sequence data are available in the GenBank database under the accession numbers hTRPA1,
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