Methyllycaconitine, alpha-bungarotoxin and (+)-tubocurarine block fast ATP-gated currents in rat dorsal root ganglion cells.
The effects of nicotinic acetylcholine receptor antagonists were studied on currents evoked by application of ATP to rat isolated dorsal root ganglion cells, and human embryonic kidney 293 cells expressing rat P2X(3) and P2X(2/3) receptors. The rapidly desensitising (within 100 ms) current in dorsal root ganglion cells was inhibited by methyllycaconitine, alpha-bungarotoxin and (+)-tubocurarine (concentrations giving half-maximal inhibition were approximately 40, 60 and 800 nm, respectively), but not by hexamethonium (100 microm) or mecamylamine (100 microm). The sustained (>250 ms) current in dorsal root ganglion cells was inhibited by (+)-tubocurarine (80% by 10 microm), but not by methyllycaconitine (200 nm), alpha-bungarotoxin (200 nm), mecamylamine (100 microm) or hexamethonium (100 microm). Rapidly desensitising currents evoked by alpha,betamethylene-ATP in human embryonic kidney cells expressing P2X(3) receptors were inhibited by methyllycaconitine and alpha-bungarotoxin, at concentrations similar to those effective in dorsal root ganglion cells. The results indicate that some nicotinic acetylcholine receptor antagonists are potent blockers of P2X receptors on neurons, particularly the homo-oligomeric P2X(3) receptor. This finding suggests that these drugs should be used with care to discriminate between P2X and neuronal acetylcholine receptor types.
Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield S10 2TN. U.Lalo@shef.ac.uk
Ulyana
U
Lalo
Yuri
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Pankratov
Oleg
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Krishtal
R Alan
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North
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058477:Receptors, Purinergic P2X3; D014403:Tubocurarine / Q000494:pharmacology*
D002038:Bungarotoxins; C546407:P2RX3 protein, human; C546410:P2rx3 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C054634:methyllycaconitine; D000255:Adenosine Triphosphate; D014403:Tubocurarine; D000157:Aconitine