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Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH

Wildman, Scott S.P., King, Brian F., Burnstock, Geoffrey (1998) Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH. British journal of pharmacology, 123 (6). pp. 1214-1220. ISSN 0007-1188. E-ISSN 1476-5381. (doi:10.1038/sj.bjp.0701717) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

1 Using recombinant P2X2 receptors expressed in Xenopus oocytes, the modulatory effects of zinc (Zn2+) on ATP-responses were studied under voltage-clamp conditions and at different levels of extracellular pH. 2 Zn2+ (0.3–300 ?M) added to the bathing medium potentiated ATP-activated membrane currents, increasing ATP-responses by up to 20 fold. This potentiating effect was reversed on washout. Zn2+-potentiation was reduced in an exponential manner (decaying 1/e in 42 s) as the interval was lengthened between adding Zn2+ then ATP to the superfusate. 3 The potentiating effect of Zn2+ was progressively diminished by acidic shifts in extracellular pH (pHe) which, of itself, also potentiated ATP-responses at P2X2 receptors. The maximal potentiating effects of Zn2+ and H+ were not additive. 4 Neither Zn2+ nor H+ potentiation of ATP-responses was abolished by diethylpyrocarbonate (DEPC, 0.3–3 mM), which irreversibly denatures histidyl residues. Nine histidyl residues are present in the extracellular loop of P2X2 receptors. 5 Zn2+ also enhanced the blocking activity of the P2 receptor antagonist suramin at P2X2 receptors. Therefore, Zn2+ also mimics H+ in increasing suramin-activity at P2X2 receptors. 6 In summary, Zn2+ and H+ potentiate agonist and antagonist activity at P2X2 receptors but their effects are not wholly alike for receptor agonism. There, the potentiating effects of Zn2+ are time-dependent and gradually convert to inhibition while those of H+ are time-independent, persistent and more potent, suggesting that either these modulators interact in a different way with a single allosteric site or with different allosteric sites.

Item Type: Article
DOI/Identification number: 10.1038/sj.bjp.0701717
Uncontrolled keywords: Zinc; extracellular pH; ATP; P2X receptor;
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 09 Dec 2015 16:39 UTC
Last Modified: 29 May 2019 16:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/52958 (The current URI for this page, for reference purposes)
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