Probenecid directly impairs activation of the canine P2X7 receptor

被引：9

作者：

Bartlett, Rachael ^{[1
,2
,3
,6
]}

Stokes, Leanne ^{[4
]}

Curtis, Stephen J. ^{[5
,7
]}

Curtis, Belinda L. ^{[5
]}

Sluyter, Ronald ^{[1
,2
,3
]}

机构：

[1] Univ Wollongong, Sch Biol Sci, Wollongong, NSW 2522, Australia

[2] Univ Wollongong, Ctr Med & Mol Biosci, Wollongong, NSW, Australia

[3] Illawarra Hlth & Med Res Inst, Wollongong, NSW, Australia

[4] Univ East Anglia, Sch Pharm, Norwich, Norfolk, England

[5] Albion Pk Vet Hosp, Albion Pk, NSW, Australia

[6] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada

[7] Compan Anim Vet Hosp, Dapto, NSW 2530, Australia

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2017年 / 36卷 / 12期

关键词：

Purinergic receptor; extracellular nucleotide; probenecid; gout; monocyte; cytokine; dog; P2X(7) RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; INTERLEUKIN-1-BETA RELEASE; SEQUESTRATION; ERYTHROCYTES; ANTAGONISTS; EXPRESSION; SECRETION; CLONING; KIDNEY;

D O I：

10.1080/15257770.2017.1391395

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The current study aimed to determine if probenecid could directly impair the canine P2X7 receptor, a ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate (ATP). Patch clamp measurements demonstrated that probenecid impairs ATP-induced inward currents in HEK-293 cells expressing canine P2X7. Flow cytometric measurements of ethidium(+) uptake into HEK-293 cells expressing canine P2X7 showed that probenecid impairs ATP-induced pore formation in a concentration-dependent manner, with a half maximal inhibitory concentration of 158 mu M. Finally, ELISA measurements revealed that probenecid impairs ATP-induced interleukin-1 beta release in dog blood. In conclusion, this study reveals that probenecid can directly impair canine P2X7 activation.

引用

页码：736 / 744

页数：9

共 36 条

[1] Unique residues in the ATP gated human P2X7 receptor define a novel allosteric binding pocket for the selective antagonist AZ10606120 [J].