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Modulatory activity of extracellular H+ and Zn2+ on ATP-responses at rP2X1 and rP2X3 receptors.

Wildman, Scott S.P., King, B. F., Burnstock, G. (1999) Modulatory activity of extracellular H+ and Zn2+ on ATP-responses at rP2X1 and rP2X3 receptors. British Journal of Pharmacology, 128 (2). pp. 486-492. ISSN 0007-1188. E-ISSN 1476-5381. (doi:10.1038/sj.bjp.0702802) (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 The modulatory activity of extracellular H+ and Zn2+ was examined on ATP-responses at rat P2X1 (rP2X1) and rat P2X3 (rP2X3) receptors expressed in Xenopus oocytes and studied under voltage-clamp conditions. 2 Superfused ATP (0.03-30 microM, at pH 7.5) evoked inward currents at rP2X1 receptors (EC50 value, 300+/-7 nM). ATP potency was reduced 2 fold at pH 6.5, and 6 fold at pH 5.5, without altering the maximum ATP effect. Alkaline conditions (pH 8.0) did not alter ATP activity. 3 Superfused ATP (0.01 - 300 microM, at pH 7. 5) evoked inward currents at rP2X3 receptors (EC50 value, 1.8+/-0.3 microM). ATP activity was affected only at pH 5.5, reducing agonist potency 15 fold without altering the maximum ATP effect. 4 Extracellular Zn2+ inhibited ATP-responses at rP2X1 receptors in a time-dependent manner, a 20 min pre-incubation being optimal (IC50 value, 1.0+/-0.2 microM). However, the Zn2+ effect was pH-independent, suggesting Zn2+- and H+-inhibition of ATP-responses occur through independent processes. 5 Extracellular Zn2+ weakly potentiated ATP-responses at rP2X3 receptors (EC50 value, 11+/-1 microM). The Zn2+ effect was dependent on pre-incubation time and, with 20 min pre-incubation periods, Zn2+ potentiated then inhibited ATP-responses in a concentration-dependent, but pH-independent, manner. 6 In summary, ATP activity at rP2X1 receptors was decreased by both extracellular H+ and Zn2+ and their effects were additive. ATP activity at rP2X3 receptors was less sensitive to H+-inhibition and, in contrast, was potentiated by Zn2+ in a pH-independent manner. These differential effects may help distinguish P2X1 and P2X3 receptors in whole tissues.

Item Type: Article
DOI/Identification number: 10.1038/sj.bjp.0702802
Uncontrolled keywords: P2X receptor; ionotropic receptor; ion channel; ATP; extracellular pH; H+; Zn2+; 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 17:01 UTC
Last Modified: 29 May 2019 16:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/52964 (The current URI for this page, for reference purposes)
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