Full sensitivity of P2X2 purinoceptor to ATP revealed by changing extracellular pH.
A full pharmacological characterization was carried out on a recombinant ATP-gated ion channel (P2X2 purinoceptor) expressed in Xenopus oocytes. This slowly-desensitizing neuronal P2X2 purinoceptor, activated by ATP (EC50 = 4.6 +/- 1 microM at pH 7.4; n = 4), showed the agonist potency order: ATP > or = 2-MeSATP = ATP gamma S > or = ATP alpha S > > Bz-ATP. The receptor affinity for ATP was enhanced 5-10 fold by acidifying the bathing solution (to pH 6.5) but was diminished 4-5 fold in an alkaline solution (pH 8.0). The maximum activity of P2X2 purinoceptors and the activity order of a series of nucleotides were unaltered by changing extracellular pH. Interestingly, ATP sensitivity at a recombinant P2Y1 purinoceptor remained unaltered with changing extracellular pH. These results indicate that acidotic conditions in the synaptic cleft could strengthen purinergic transmission at neuronal P2X2 purinoceptors.
King
B F
BF
Department of Anatomy and Developmental Biology, University College London.
Ziganshina
L E
LE
Pintor
J
J
Burnstock
G
G
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003470:Culture Media; D006863:Hydrogen-Ion Concentration; D009479:Neuropeptides / Q000819:agonists / Q000378:metabolism*; D009865:Oocytes; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D014422:Turkeys; D014982:Xenopus laevis
D003470:Culture Media; D009479:Neuropeptides; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D000255:Adenosine Triphosphate