Characteristics of ATP-induced current through P2X7 receptor in NG108-15 cells: unique antagonist sensitivity and lack of pore formation.
ATP activates the mouse P2X7 receptor and induces a nonselective-cation current in NG108-15 cells. We investigated the effects of five receptor antagonists on the ATP-induced nonselective-cation current through P2X7 receptor (I(NS.P2X7)) in NG108-15 cells. Nonselective P2 receptor antagonists, RB-2, PPADS and suramin inhibited the I(NS.P2X7) with IC50 values of 4.3, 53 and 40 microM, respectively. However, KN-04, which is a potent antagonist of human P2X7 receptors but is not that of rat P2X7 receptors, had only a weak blocking effect. Furthermore, oxidized-ATP (300 microM), an antagonist of the P2X7 receptor-mediated pore-formation, did not affect the I(NS.P2X7). Prolonged ATP application did not increase the membrane permeability to large molecules, N-methyl-D-glucamine or Yo-Pro-1, indicating that pore-formation was not promoted by the P2X7 receptor activation in NG108-15 cells. These results suggest that antagonist sensitivities and pore-forming properties of the P2X7 receptors in NG108-15 cells are different from those of other cells types.
Watano
Tomokazu
T
Department of Pharmacology, Fukushima Medical University School of Medicine, Japan.
Matsuoka
Isao
I
Kimura
Junko
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001583:Benzoxazoles; D002412:Cations; D002463:Cell Membrane Permeability; D005456:Fluorescent Dyes / Q000378:metabolism; D051379:Mice; D018408:Patch-Clamp Techniques; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D011806:Quinolinium Compounds; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001583:Benzoxazoles; D002412:Cations; D005456:Fluorescent Dyes; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D011806:Quinolinium Compounds; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D014227:Triazines; C065344:KN 04; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C089813:YO-PRO 1; C017199:2',3'-dialdehyde ATP; C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D013498:Suramin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate