title: The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs.
abstract: 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 IC(50) of 32.5 μm. Capsaicin and its analogs are thus useful tools for physiological analysis of PKD1L3/PKD2L1 function.
authors.affiliation: Central Research Institute, Mizkan Group Co., Handa, Aichi, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Ishii
authors.forename: Azusa
authors.initials: A
authors.lastname: Kurokawa
authors.forename: Mikiya
authors.initials: M
authors.lastname: Kishi
authors.forename: Keigo
authors.initials: K
authors.lastname: Yamagami
authors.forename: Shinji
authors.initials: S
authors.lastname: Okada
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishimaru
authors.forename: Takumi
authors.initials: T
authors.lastname: Misaka
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology*; D050396:TRPP Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013650:Taste Buds / Q000187:drug effects; D014059:Tongue / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C512453:PKD1L3 protein, mouse; C486487:Pkd2l1 protein, mouse; D011956:Receptors, Cell Surface; D018689:Sensory System Agents; D050396:TRPP Cation Channels; D002211:Capsaicin