Premium
Actions of general anaesthetics on 5‐HT 3 receptors in N1E‐115 neuroblastoma cells
Author(s) -
Jenkins A.,
Franks N.P.,
Lieb W.R.
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.tb15314.x
Subject(s) - methoxyflurane , halothane , isoflurane , chemistry , minimum alveolar concentration , enflurane , membrane potential , 5 ht receptor , receptor , biophysics , anesthesia , serotonin , biochemistry , medicine , biology , organic chemistry
1 N1E‐115 mouse neuroblastoma cells were studied under voltage clamp in the whole‐cell patch‐clamp configuration. Peak currents induced by bath application of 5‐hydroxytryptamine (5‐HT) were inwardly rectifying, reversed at 0.4 ± 0.2 mV (mean ± s.e.mean), and were approximately half‐inhibited (at 1 μ m 5‐HT) by 2 nM of the 5‐HT 3 selective antagonist MDL‐72222 (3‐tropanyl‐3,5‐dichlorobenzoate). 2 Peak inward currents activated by a low concentration of 5‐HT at a holding potential of −50 mV were potentiated by volatile general anaesthetics. At their human minimum alveolar concentrations (MACs), the degree of potentiation increased in the order isoflurane < halothane < enflurane < methoxyflurane. Potentiation by methoxyflurane was independent of membrane potential in the range −70 mV to +40 mV. The reversal potential was the same in the presence and absence of methoxyflurane. 3 Methoxyflurane shifted the 5‐HT dose‐response curve to lower 5‐HT concentrations, without significantly changing the Hill coefficient or maximum response. The EC 50 concentration for 5‐HT decreased from 1.86 ± 0.02 μ m to 1.07 ± 0.11 μ m (means ± s.e.mean) due to the presence of 1 MAC (270 μ m ) methoxyflurane. 4 In contrast to the volatile anaesthetics, the barbiturate anaesthetic, thiopentone, inhibited the 5‐HT 3 receptor. Hill analysis of thiopentone dose‐response data gave an average IC 50 = 117 ± 8 μ m thiopentone and Hill coefficient = 1.6 ± 0.2 (means ± s.e.mean). These parameters were not significantly different for data obtained at 5‐HT concentrations above and below the control EC 50 concentration for 5‐HT, consistent with non‐competitive inhibition. 5 The n ‐alcohols occupied an intermediate position between the volatile and barbiturate anaesthetics. The lower alcohols (butanol and hexanol) potentiated 5‐HT responses at low alcohol concentrations but inhibited them at high concentrations. In contrast, the higher alcohols (octanol, decanol, dodecanol, tridecanol, tetradecanol and pentadecanol) produced no potentiation, but only inhibition, at all alcohol concentrations. 6 Inhibition of the 5‐HT 3 receptor by the n ‐alcohols exhibited a cutoff in potency similar to those previously found for tadpoles, luciferase enzymes and a neuronal nicotinic acetylcholine receptor channel.