P2X4: an ATP-activated ionotropic receptor cloned from rat brain.
Extracellular ATP exerts pronounced biological actions in virtually every organ or tissue that has been studied. In the central and peripheral nervous system, ATP acts as a fast excitatory transmitter in certain synaptic pathways [Evans, R.J., Derkach, V. & Surprenant, A. (1992) Nature (London) 357, 503-505; Edwards, F.A., Gigg, A.J. & Colquhoun, D. (1992) Nature (London) 359, 144-147]. Here, we report the cloning and characterization of complementary DNA from rat brain, encoding an additional member (P2X4) of the emerging multigenic family of ligand-gated ATP channels, the P2X receptors. Expression in Xenopus oocytes gives an ATP-activated cation-selective channel that is highly permeable to Ca2+ and whose sensitivity is modulated by extracellular Zn2+. Surprisingly, the current elicited by ATP is almost insensitive to the common P2X antagonist suramin. In situ hybridization reveals the expression of P2X4 mRNA in central nervous system neurons. Northern blot and reverse transcription-PCR (RT-PCR) analysis demonstrate a wide distribution of P2X4 transcripts in various tissues, including blood vessels and leukocytes. This suggests that the P2X4 receptor might mediate not only ATP-dependent synaptic transmission in the central nervous system but also a wide repertoire of biological responses in diverse tissues.
Soto
F
F
Department of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Gottingen, Germany.
Garcia-Guzman
M
M
Gomez-Hernandez
J M
JM
Hollmann
M
M
Karschin
C
C
Stühmer
W
W
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009865:Oocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014982:Xenopus laevis
D017931:DNA Primers; D018076:DNA, Complementary; C548228:P2rx4 protein, rat; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D002118:Calcium