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    SyncroPatch 384: HTS Automated Patch Clamp

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    SURFE²R 96SE: 非标记高通量转运体筛选

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    Dynamic Clamp: Patchliner

  • 脂双层记录: Orbit产品系列

    脂双层记录: Orbit产品系列

  • CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

    CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

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2012 - TRPA1 Agonist Activity of Probenecid Desensitizes Channel Responses: Consequences for Screening

icon pl   Patchliner publication in ASSAY and Drug Development Technologies (2012)

Authors: 
McClenaghan C., Zeng F., Verkuyl J.M.

 

Journal: 
Assay Drug Dev Technol. (2012) 10(6):533-541


Abstract: 

The transient receptor potential channel subtype A member 1 (TRPA1) is a nonselective cation channel widely viewed as having therapeutic potential, particularly for pain-related indications. Realization of this potential will require potent, selective modulators; however, currently the pharmacology of TRPA1 is poorly defined. As TRPA1 is calcium permeable, calcium indicators offer a simple assay format for high-throughput screening. In this report, we show that probenecid, a uricosuric agent used experimentally in screening to increase loading of calcium-sensitive dyes, activates TRPA1. Prolonged probenecid incubation during the dye-loading process reduces agonist potency upon subsequent challenge. When Chinese Hamster Ovary (CHO)-hTRPA1 or STC-1 cells, which endogenously express TRPA1, were dye loaded in the presence of 2 mM probenecid TRPA1, agonists appeared less potent; EC(50) for allyl isothiocyante agonists in CHO-hTRPA1 was increased from 1.5±0.19 to 7.32±1.20 μM (P<0.01). No significant effect on antagonist potency was observed when using the agonist EC(80) concentration determined under the appropriate dye-loading conditions. We suggest an alternative protocol for calcium imaging using another blocker of anion transport, sulfinpyrazone. This blocker significantly augments indicator dye loading and the screening window, but is not a TRPA1 agonist and has no effect on agonist potency.


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