TY - JOUR
T1 - σ-Binding site ligands inhibit K+ currents in rat locus coeruleus neurons in vitro
AU - Nguyen, Vu H.
AU - Ingram, Susan L.
AU - Kassiou, Michael
AU - J. Christie, MacDonald
N1 - Funding Information:
Supported by the National Health and Medical Research Council of Australia. S.L. Ingram was supported by a Human Frontier Science Fellowship and MJ Christie by the Medical Foundation of The University of Sydney.
PY - 1998/11/13
Y1 - 1998/11/13
N2 - Biological actions of novel σ1- and σ2-selective binding site ligands (trishomocubanes: 4-azahexacyclo [5.4.1.0.2,6.03,10.05,9.08,11]dodecanes), and the reference ligands, 1,3-di(2-tolyl)-guanidine (DTG), haloperidol, (+)-pentazocine and dextromethorphan, were studied in rat locus coeruleus neurons using intracellular and whole-cell patch clamp recordings. High concentrations of trishomocubanes produced small inward currents and affected some parameters of action potential waveforms suggesting modest potency to inhibit ionic conductances underlying action potentials. σ-Ligands produced large inward currents in the presence of μ-opioid, α2-adrenoceptor and ORL1 receptor agonists. These reversed polarity near the K+ equilibrium potential, suggesting that σ-ligands act as ligand activated K+-channel blockers or interfere with the coupling between these receptors and K+-channels. However, no correlation was found between binding affinities at σ1- or σ2-binding sites and potency to inhibit K+-currents, suggesting that these effects on K+-channels are not directly related to occupancy of σ binding sites. Copyright (C) 1998 Elsevier Science B.V.
AB - Biological actions of novel σ1- and σ2-selective binding site ligands (trishomocubanes: 4-azahexacyclo [5.4.1.0.2,6.03,10.05,9.08,11]dodecanes), and the reference ligands, 1,3-di(2-tolyl)-guanidine (DTG), haloperidol, (+)-pentazocine and dextromethorphan, were studied in rat locus coeruleus neurons using intracellular and whole-cell patch clamp recordings. High concentrations of trishomocubanes produced small inward currents and affected some parameters of action potential waveforms suggesting modest potency to inhibit ionic conductances underlying action potentials. σ-Ligands produced large inward currents in the presence of μ-opioid, α2-adrenoceptor and ORL1 receptor agonists. These reversed polarity near the K+ equilibrium potential, suggesting that σ-ligands act as ligand activated K+-channel blockers or interfere with the coupling between these receptors and K+-channels. However, no correlation was found between binding affinities at σ1- or σ2-binding sites and potency to inhibit K+-currents, suggesting that these effects on K+-channels are not directly related to occupancy of σ binding sites. Copyright (C) 1998 Elsevier Science B.V.
KW - K channel
KW - Locus coeruleus
KW - Nociceptin
KW - Opioid
KW - Trishomocubane
KW - σ Receptor
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U2 - 10.1016/S0014-2999(98)00706-7
DO - 10.1016/S0014-2999(98)00706-7
M3 - Article
C2 - 9851553
AN - SCOPUS:0031754089
SN - 0014-2999
VL - 361
SP - 157
EP - 163
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -