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Modulation of ATP-responses at recombinant rP2X4 receptors by extracellular pH and zinc.

Wildman, Scott S.P., King, B. F., Burnstock, G. (1999) Modulation of ATP-responses at recombinant rP2X4 receptors by extracellular pH and zinc. British Journal of Pharmacology, 126 (3). pp. 762-768. ISSN 0007-1188. E-ISSN 1476-5381. (doi:10.1038/sj.bjp.0702325) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

The modulatory effects of extracellular H+ and Zn2+ were tested against ATP-responses at rat P2X4 (rP2X4) receptors expressed in Xenopus oocytes under voltage-clamp conditions. ATP (0.1-100 microM, at pH 7.5), evoked inward currents via rP2X4 receptors (EC50 value, 4.1+/-0.98 microM; nH, 1.2+/-0.1). ATP potency was reduced 2 fold, at pH 6.5, without altering maximal activity. ATP potency was reduced by a further 4 fold, at pH 5.5, and the maximal activity of ATP was also reduced. Alkaline conditions (pH 8.0) had no effect on ATP-responses. Zn2+ (100 nM - 10 microM) potentiated ATP-responses at the rP2X4 receptor by 2 fold, whereas higher concentrations (30 microM - 1 mM) inhibited ATP-responses. Zn2+ potentiation was due to an increase in ATP potency, whereas its inhibitory action was due to a reduction in ATP efficacy. Zn2+ modulation of ATP-responses was pH-dependent. At pH 6.5, the bell-shaped curve for Zn2+ was shifted to the right by 1 log unit. At pH 5.5, Zn2+ potentiation was abolished and its inhibitory effect reduced considerably. Suramin (50 microM) also potentiated ATP-responses at rP2X4 receptors. Neither H+ (pH 6.5 and 5.5), Zn2+ (10-100 microM) or a combination of both failed to reveal an inhibitory action of suramin at rP2X4 receptors. In conclusion, H+ and Zn2+ exerted opposite effects on the rP2X4 receptor by lowering and raising agonist potency, respectively. H+ (> or = 3 microM) and Zn2+ (> or = 30 microM) also reduces agonist efficacy by lowering the number of rP2X4 receptors available for activation. The striking differences between the modulatory actions of H+ and Zn2+ at rP2X4 and rP2X2 receptors are discussed.

Item Type: Article
DOI/Identification number: 10.1038/sj.bjp.0702325
Uncontrolled keywords: Extracellular pH; zinc; ATP; P2X receptor; Xenopus oocyte
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Scott S.P. Wildman
Date Deposited: 09 Dec 2015 17:07 UTC
Last Modified: 29 May 2019 16:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/52965 (The current URI for this page, for reference purposes)
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