Abstract
We have cloned P2X4, a member of the P2-purinoceptor family, which has a new pharmacological profile. Rat P2X4 is distantly related to P2X1, P2X2 and P2X3 and is expressed in brain, spinal cord, lung, thymus, bladder, adrenal, testis and vas deferens. This ligand gated ion channel is activated by ATP and analogs with the potency order of ATP > ATP gamma S > 2-methylthio ATP > ADP approximately alpha beta-methylene ATP. However, none of the currently used P2X purinoceptor antagonists suramin, reactive blue 2 and PPADS blocked ATP evoked currents; in contrast their application resulted in potentiation of the agonist response. Due to lack of any known antagonist for P2X4 it is unlikely that native P2X4 has previously been recognized as a P2X purinoceptor.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives*
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Adenosine Triphosphate / pharmacology*
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Adrenal Glands / metabolism
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Amino Acid Sequence
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Animals
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Brain / metabolism*
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Conserved Sequence
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Cysteine
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DNA, Complementary
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Female
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Hippocampus / metabolism
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In Situ Hybridization
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Ion Channel Gating
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Ion Channels / biosynthesis
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Ion Channels / drug effects
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Ion Channels / physiology*
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Kinetics
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Lung / metabolism
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Male
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Oocytes / drug effects
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Oocytes / physiology
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Organ Specificity
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Rats
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Receptors, Purinergic P2 / biosynthesis
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Receptors, Purinergic P2 / drug effects
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Receptors, Purinergic P2 / physiology*
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Receptors, Purinergic P2X4
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Sequence Homology, Amino Acid
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Spinal Cord / metabolism*
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Suramin / pharmacology
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Testis / metabolism
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Thymus Gland / metabolism
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Vas Deferens / metabolism
Substances
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DNA, Complementary
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Ion Channels
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P2rx4 protein, rat
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Receptors, Purinergic P2
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Receptors, Purinergic P2X4
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Suramin
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Adenosine Triphosphate
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Cysteine