气候变化领域集成服务门户(CCPortal): Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC

CCPortal

DOI	10.1073/pnas.2108094118
	Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC
	Fong Z.; Griffin C.S.; Large R.J.; Hollywood M.A.; Thornbury K.D.; Sergeant G.P.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:37
英文摘要	P2X1 receptors are adenosine triphosphate (ATP)-gated cation channels that are functionally important for male fertility, bladder contraction, and platelet aggregation. The activity of P2X1 receptors is modulated by lipids and intracellular messengers such as cAMP, which can stimulate protein kinase A (PKA). Exchange protein activated by cAMP (EPAC) is another cAMP effector; however, its effect on P2X1 receptors has not yet been determined. Here, we demonstrate that P2X1 currents, recorded from human embryonic kidney (HEK) cells transiently transfected with P2X1 cDNA, were inhibited by the highly selective EPAC activator 007-AM. In contrast, EPAC activation enhanced P2X2 current amplitude. The PKA activator 6-MB-cAMP did not affect P2X1 currents, but inhibited P2X2 currents. The inhibitory effects of EPAC on P2X1 were prevented by triple mutation of residues 21 to 23 on the amino terminus of P2X1 subunits to the equivalent amino acids on P2X2 receptors. Double mutation of residues 21 and 22 and single mutation of residue 23 also protected P2X1 receptors from inhibition by EPAC activation. Finally, the inhibitory effects of EPAC on P2X1 were also prevented by NSC23766, an inhibitor of Rac1, a member of the Rho family of small GTPases. These data suggest that EPAC is an important regulator of P2X1 and P2X2 receptors. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CAMP; EPAC; P2X1
语种	英语
scopus关键词	4 amino 6 [2 [[4 (diethylamino) 1 methylbutyl]amino] 6 methyl 4 pyrimidinyl] 2 methylquinoline; adenosine triphosphate; aminoquinoline derivative; cyclic AMP; cyclic AMP dependent protein kinase; guanine nucleotide exchange factor; purinergic P2X1 receptor; purinergic P2X2 receptor; pyrimidine derivative; Rac1 protein; RAC1 protein, human; RAPGEF3 protein, human; drug effect; gene expression regulation; genetics; HEK293 cell line; human; kidney; metabolism; Adenosine Triphosphate; Aminoquinolines; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Gene Expression Regulation; Guanine Nucleotide Exchange Factors; HEK293 Cells; Humans; Kidney; Pyrimidines; rac1 GTP-Binding Protein; Receptors, Purinergic P2X1; Receptors, Purinergic P2X2
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251019
作者单位	Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, A91 K584, Ireland
推荐引用方式 GB/T 7714	Fong Z.,Griffin C.S.,Large R.J.,et al. Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC[J],2021,118(37).
APA	Fong Z.,Griffin C.S.,Large R.J.,Hollywood M.A.,Thornbury K.D.,&Sergeant G.P..(2021).Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC.Proceedings of the National Academy of Sciences of the United States of America,118(37).
MLA	Fong Z.,et al."Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC".Proceedings of the National Academy of Sciences of the United States of America 118.37(2021).