Properties of Ca2+ release-activated Ca2+ channel block by 5-nitro-2-(3-phenylpropylamino)-benzoic acid in Jurkat cells
| Autor: | Jack H. Li, Edward P. Christian, Katherine T. Spence, Pauline G. Dargis |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Pharmacology
Patch-Clamp Techniques Stereochemistry Kinetics chemistry.chemical_element Hydrogen-Ion Concentration Calcium Chloride channel blocker Calcium Channel Blockers Jurkat cells Electric Stimulation In vitro Electrophysiology Jurkat Cells chemistry Chloride Channels Nitrobenzoates Extracellular Biophysics Humans Calcium Channels Patch clamp Intracellular |
| Zdroj: | European Journal of Pharmacology. 394:171-179 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(00)00144-8 |
| Popis: | Ca(2+) release-activated Ca(2+) current (I(crac)) has been previously characterized biophysically in Jurkat lymphocytes and other non-excitable cells, but pharmacology remains poorly developed. The present objective was to delineate with whole cell recording details of the interaction of the chloride channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), with I(crac) in Jurkat cells. NPPB reversibly inhibited I(crac) in a concentration-dependent manner (IC(50)=5 microM). Kinetics for block and unblock of I(crac) by NPPB indicated a bimolecular interaction. Michaelis-Menten analysis indicated that NPPB interacts competitively with extracellular Ca(2+) permeating the I(crac) pathway. Finally, analysis of the pH dependence of I(crac) block by NPPB revealed a reduction in the apparent affinity during extracellular alkalinization that based on the pK(a) for NPPB, suggested that the neutral form of NPPB blocks the Ca(2+) release-activated Ca(2+) (CRAC) channel. Taken together, our results suggest a direct interaction between NPPB and the CRAC channel, and should help guide insights for developing novel and more selective analogues. |
| Databáze: | OpenAIRE |
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