Details

Autor(en) / Beteiligte

• Robertson, S.J.
• Rae, M.G.
• Rowan, E.G.
• Kennedy, C.

Titel

Characterization of a P2X‐purinoceptor in cultured neurones of the rat dorsal root ganglia

Ist Teil von

• British journal of pharmacology, 1996-06, Vol.118 (4), p.951-956

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

1996

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 1 The electrophysiological actions of the P2‐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 μm) 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 EC50 of 719 nM and a Hill slope of 1.47. 3 2‐meSATP (10 nM‐100 μm) and α, μ‐meATP (100 nM‐100 μm) also evoked transient inward currents. The EC50 and Hill slopes were 450 nM and 1.58 for 2‐meSATP and 1.95 μm 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 μm 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 P2‐purinoceptor antagonist, suramin (100 μm). 6 UTP (10 μm) evoked similar transient inward currents, which were sensitive to suramin (100 μm). ATP (10 μm), applied 2 min beforehand, reduced the response to UTP (10 μm) by 80 ± 10%. 7 This study shows that ATP, 2‐meSATP and α, μ‐meATP act via a suramin‐sensitive P2X‐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 P2X3‐subtype to produce these effects.