Effects of neuroamines and divalent cations on cloned and mutated ATP-gated channels.
Sensitivities to dopamine, 5-hydroxytryptamine, Zn2+ and Cd2+ were studied in P2X1, P2X2, P2X3 and P2X4 purinoceptors and mutants of P2X2 purinoceptors expressed in Xenopus oocytes. Dopamine (10 and 100 microM) and 5-hydroxytryptamine (1 to 100 microM) enhanced the inward current activated by extracellular ATP through P2X2 and P2X4 purinoceptors. Zn2+ (1 to 100 microM) and Cd2+ (10 microM to 1 microM) enhanced the current through P2X2 purinoceptors. As for P2X4 purinoceptors, the ATP-activated current was, however, enhanced after the washout of Zn2+ (100 microM) or Cd2+ (1 mM). Three mutants of P2X2 purinoceptors were constructed by substituting negatively charged amino-acid residues. The magnitude of the enhancement by Zn2+, Cd2+ and dopamine was attenuated when Asp221 was replaced by histidine. The results suggest that dopamine, Zn2+ and Cd2+ require some common motif for the current enhancement.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, Setagaya, Tokyo, Japan.
Ohno
Y
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D003001:Cloning, Molecular; D004298:Dopamine / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009865:Oocytes / Q000502:physiology / Q000648:ultrastructure; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D014981:Xenopus / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*
D018048:Receptors, Purinergic P2; D002104:Cadmium; D012701:Serotonin; D000255:Adenosine Triphosphate; D015032:Zinc; D004298:Dopamine