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Characterization of a P 2X ‐purinoceptor in cultured neurones of the rat dorsal root ganglia
Author(s) -
Robertson S.J.,
Rae M.G.,
Rowan E.G.,
Kennedy C.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15491.x
Subject(s) - suramin , biophysics , electrophysiology , antagonist , biology , adenosine triphosphate , adenosine , purinergic receptor , medicine , anatomy , endocrinology , biochemistry , receptor , neuroscience
1 The electrophysiological actions of the P 2 ‐purinoceptor agonists, adenosine 5′‐triphosphate (ATP), 2‐methylthioATP (2‐meSATP) and α, β‐methyleneATP (α, β‐meATP) and of uridine 5′‐triphosphate (UTP) were studied under concentration and voltage‐clamp conditions in dissociated neurones of 1–6 day old rat dorsal root ganglia. 2 ATP (10 nM‐100 μ m ) applied rapidly via a U‐tube perfusion system (equilibration time > 10 ms) activated concentration‐dependent inward currents with a latency to onset of a few ms, an EC 50 of 719 nM and a Hill slope of 1.47. 3 2‐meSATP (10 nM‐100 μ m ) and α, μ‐meATP (100 nM‐100 μ m ) also evoked transient inward currents. The EC 50 and Hill slopes were 450 nM and 1.58 for 2‐meSATP and 1.95 μ m and 1.53 for α, μ‐meATP respectively. There was no significant difference between the maximum currents evoked by the three agonists. 4 As the concentration of ATP increased so the rate of rise and decay of the currents also increased. At 100 and 300 nM ATP the decay of the current was best fitted by a single exponential, but at 1 μ m and above two exponentials were required. Log‐log plots of the rise time or time constants of decay versus concentration were linear. Currents evoked by 2‐meSATP and α, μ‐meATP showed a similar concentration‐dependence in their kinetics. 5 Inward currents evoked by ATP, 2‐meSATP and α, μ‐meATP (300 nM) were abolished by the P 2 ‐purinoceptor antagonist, suramin (100 μ m ). 6 UTP (10 μ m ) evoked similar transient inward currents, which were sensitive to suramin (100 μ m ). ATP (10 μ m ), applied 2 min beforehand, reduced the response to UTP (10 μ m ) by 80 ± 10%. 7 This study shows that ATP, 2‐meSATP and α, μ‐meATP act via a suramin‐sensitive P 2X ‐purinoceptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The pyrimidine nucleotide, UTP, was also active. It is likely that the agonists were acting at the P 2X3 ‐subtype to produce these effects.