An Antagonist-insensitive P2X Receptor Expressed in Epithelia and Brain

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Jan 2

PMID 8598206

Citations 120

Authors

G Buell

C Lewis

G Collo

R A North

A Surprenant

Affiliations

Soon will be listed here.

Abstract

A cDNA was cloned which encodes a new ATP-gated ion channel (P2X4 receptor). ATP induces a cationic current in HEK293 cells transfected with the P2X4 receptor. However, the current is almost completely insensitive to antagonists effective at other P2X receptors. Sensitivity to two of these antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and pyridoxal 5-phosphate) is restored by replacement of Glu249 by lysine, which occurs at the equivalent position in P2X1 and P2X2 receptors. P2X4 RNA is found by in situ hybridization in the brain, peripheral ganglia and epithelia including serosal cells of salivary glands. Recordings from rat submandibular gland cells showed ATP-induced currents that are also insensitive to antagonists. These results define a further member of P2X receptor family, and they identify an amino acid residue involved in antagonist binding. They also introduce a new phenotype for ATP responses at P2X receptors--insensitivity to currently known antagonists.

Citing Articles

Structural insights into the orthosteric inhibition of P2X receptors by non-ATP analog antagonists.

Sheng D, Yue C, Jin F, Wang Y, Ichikawa M, Yu Y Elife. 2024; 12.

PMID: 38578670 PMC: 10997329. DOI: 10.7554/eLife.92829.

Purinoceptors in the Central Nervous System.

Dunwiddie T, Abbracchio M, Bischofberger N, Brundege J, Buell G, Collo G Drug Dev Res. 2024; 39(3-4):361-370.

PMID: 38283105 PMC: 10821783. DOI: 10.1002/(sici)1098-2299(199611/12)39:3/4<361::aid-ddr17>3.0.co;2-4.

Structural insights into the allosteric inhibition of P2X4 receptors.

Shen C, Zhang Y, Cui W, Zhao Y, Sheng D, Teng X Nat Commun. 2023; 14(1):6437.

PMID: 37833294 PMC: 10575874. DOI: 10.1038/s41467-023-42164-y.

Migraine signaling pathways: purine metabolites that regulate migraine and predispose migraineurs to headache.

Biringer R Mol Cell Biochem. 2023; 478(12):2813-2848.

PMID: 36947357 DOI: 10.1007/s11010-023-04701-7.

The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.

Sophocleous R, Ooi L, Sluyter R Int J Mol Sci. 2022; 23(10).

PMID: 35628550 PMC: 9147237. DOI: 10.3390/ijms23105739.

References

Kasakov L, Burnstock G . The use of the slowly degradable analog, alpha, beta-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder. Eur J Pharmacol. 1982; 86(2):291-4. DOI: 10.1016/0014-2999(82)90330-2. View

Fenwick E, Marty A, Neher E . A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol. 1982; 331:577-97. PMC: 1197770. DOI: 10.1113/jphysiol.1982.sp014393. View

Sneddon P, Westfall D . Pharmacological evidence that adenosine triphosphate and noradrenaline are co-transmitters in the guinea-pig vas deferens. J Physiol. 1984; 347:561-80. PMC: 1199464. DOI: 10.1113/jphysiol.1984.sp015083. View

Dunn P, BLAKELEY A . Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol. 1988; 93(2):243-5. PMC: 1853806. DOI: 10.1111/j.1476-5381.1988.tb11427.x. View

Sasaki T, Gallacher D . Extracellular ATP activates receptor-operated cation channels in mouse lacrimal acinar cells to promote calcium influx in the absence of phosphoinositide metabolism. FEBS Lett. 1990; 264(1):130-4. DOI: 10.1016/0014-5793(90)80782-e. View

Evans R, Derkach V, Surprenant A . ATP mediates fast synaptic transmission in mammalian neurons. Nature. 1992; 357(6378):503-5. DOI: 10.1038/357503a0. View

Vincent P . Cationic channels sensitive to extracellular ATP in rat lacrimal cells. J Physiol. 1992; 449:313-31. PMC: 1176081. DOI: 10.1113/jphysiol.1992.sp019088. View

Edwards F, Gibb A, Colquhoun D . ATP receptor-mediated synaptic currents in the central nervous system. Nature. 1992; 359(6391):144-7. DOI: 10.1038/359144a0. View

Evans R, Surprenant A . Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP. Br J Pharmacol. 1992; 106(2):242-9. PMC: 1907483. DOI: 10.1111/j.1476-5381.1992.tb14323.x. View

10.

Ueno S, HARATA N, Inoue K, Akaike N . ATP-gated current in dissociated rat nucleus solitarii neurons. J Neurophysiol. 1992; 68(3):778-85. DOI: 10.1152/jn.1992.68.3.778. View

11.

Cloues R, Jones S, Brown D . Zn2+ potentiates ATP-activated currents in rat sympathetic neurons. Pflugers Arch. 1993; 424(2):152-8. DOI: 10.1007/BF00374606. View

12.

Ziganshin A, Hoyle C, Bo X, Lambrecht G, Mutschler E, Baumert H . PPADS selectively antagonizes P2X-purinoceptor-mediated responses in the rabbit urinary bladder. Br J Pharmacol. 1993; 110(4):1491-5. PMC: 2175839. DOI: 10.1111/j.1476-5381.1993.tb13990.x. View

13.

Schaeren-Wiemers N . A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes. Histochemistry. 1993; 100(6):431-40. DOI: 10.1007/BF00267823. View

14.

Traut T . The functions and consensus motifs of nine types of peptide segments that form different types of nucleotide-binding sites. Eur J Biochem. 1994; 222(1):9-19. DOI: 10.1111/j.1432-1033.1994.tb18835.x. View

15.

Hurley T, Ryan M, Shoemaker D . Mobilization of Ca2+ influx, but not of stored Ca2+, by extracellular ATP in rat submandibular gland acini. Arch Oral Biol. 1994; 39(3):205-12. DOI: 10.1016/0003-9969(94)90046-9. View

16.

Valera S, Hussy N, Evans R, Adami N, North R, Surprenant A . A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP. Nature. 1994; 371(6497):516-9. DOI: 10.1038/371516a0. View

17.

Brake A, Wagenbach M, Julius D . New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature. 1994; 371(6497):519-23. DOI: 10.1038/371519a0. View

18.

Trezise D, Bell N, Khakh B, Michel A, Humphrey P . P2 purinoceptor antagonist properties of pyridoxal-5-phosphate. Eur J Pharmacol. 1994; 259(3):295-300. DOI: 10.1016/0014-2999(94)90656-4. View

19.

Galligan J, Bertrand P . ATP mediates fast synaptic potentials in enteric neurons. J Neurosci. 1994; 14(12):7563-71. PMC: 6576907. View

20.

Zimmermann H . Signalling via ATP in the nervous system. Trends Neurosci. 1994; 17(10):420-6. DOI: 10.1016/0166-2236(94)90016-7. View