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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | King, B. F. Wildman, S. S. Burnstock, G. |
| Description | Author Affiliation: Wildman SS ( Autonomic Neuroscience Institute, Royal Free Hospital School of Medicine, University College London, England.) |
| 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Pharmacology Receptors, Purinergic P2 Drug Effects Zinc Animals Dose-Response Relationship, Drug Drug Synergism Hydrogen-Ion Concentration Membrane Potentials Oocytes Purinergic P2 Receptor Antagonists Receptors, Purinergic P2X4 Recombinant Proteins Suramin Xenopus Laevis Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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