Abstract:
BACKGROUND AND PURPOSE:Heat-sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are indispensable in the formation of the glomerular filtration barrier, we investigated the presence and function of Ca2+ -permeable TRPV1-4 channels in human podocyte cultures. EXPERIMENTAL APPROACH:Expression of TRPV1-4 channels was investigated at protein (immunocytochemistry, Western blot) and mRNA (Q-PCR) level in a conditionally immortalized human podocyte cell line. Channel function was assessed by measuring intracellular Ca2+ concentration using Flou-4 Ca2+ -indicator dye and patch clamp electrophysiology upon applying various activators and inhibitors. KEY RESULTS:Thermosensitive TRP channels were expressed in podocytes. The TRPV1-specific agonists capsaicin and resiniferatoxin did not affect the intracellular Ca2+ concentration. Cannabidiol, an activator of TRPV2 and TRPV4 channels, induced moderate Ca2+ -influxes, inhibited by both tranilast and HC067047, blockers of TRPV2 and TRPV4 channels respectively. The TRPV4-specific agonists GSK1016790A and 4α-phorbol 12,13-didecanoate induced robust Ca2+ -signals which were abolished by HC067047. Non-specific agonists of TRPV3 channels induced marked Ca2+ transients. However, TRPV3 channel blockers, ruthenium red and isopentenyl diphosphate only partly inhibited the responses and TRPV3 silencing was ineffective suggesting remarkable off-target effects of the compounds. CONCLUSION AND IMPLICATIONS:Our results indicate the functional presence of TRPV4 and other thermosensitive TRPV channels in human podocytes and raise the possibility of their involvement in the regulation of glomerular filtration barrier.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ambrus L,Kelemen B,Szabó T,Bíró T,Tóth BIdoi
10.1111/bph.14052subject
Has Abstractpub_date
2017-12-01 00:00:00pages
4493-4507issue
23eissn
0007-1188issn
1476-5381journal_volume
174pub_type
杂志文章abstract::1. The drug HA-966 (1-hydroxy-3-amino-pyrrolidone-2), which chemically resembles the cyclic form of GABA, has been studied for neuro-pharmacological properties and for effects on the catecholamine content of the corpus striatum.2. The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and rev...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07182.x
更新日期:1971-11-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12638
更新日期:2014-09-01 00:00:00
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更新日期:2005-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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journal_title:British journal of pharmacology
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abstract::1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been inves...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16348.x
更新日期:1995-06-01 00:00:00
abstract::1. Nicotine can activate primary afferent nociceptors, one result of which is to increase neurogenic plasma extravasation. In this study we have demonstrated a novel proinflammatory effect of sub-nanomolar nicotine, mediated by peripheral action at sensory neurons. This action is normally masked by adrenal medulla-der...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704031
更新日期:2001-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1991-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13528.x
更新日期:1993-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2017-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10031.x
更新日期:1983-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14324.x
更新日期:1992-06-01 00:00:00
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更新日期:2000-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12751.x
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doi:10.1038/sj.bjp.0705263
更新日期:2003-05-01 00:00:00
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更新日期:2003-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0702983
更新日期:2000-01-01 00:00:00
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pub_type: 社论
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更新日期:2009-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15520.x
更新日期:1996-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703365
更新日期:2000-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09553.x
更新日期:1970-05-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13977.x
更新日期:1993-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701575
更新日期:1998-01-01 00:00:00