TY - JOUR
T1 - A patch clamp study of the effects of ciprofloxacin and biphenyl acetic acid on rat hippocampal neurone GABAA and lonotropic glutamate receptors
AU - Halliwell, R. F.
AU - Davey, P. G.
AU - Lambert, J. J.
PY - 1995/12
Y1 - 1995/12
N2 - The neurotoxic effects of 4-quinolones alone and in combination with certain non-steroidal anti-inflammatory drugs (NSAIDs) may be related to an interaction at GABAA and/or ionotropic glutamate receptors. In the present study, the effects of the fluoroquinolone, ciprofloxacin, alone and in combination with the NSAID, biphenyl acetic acid (BPAA), were examined on GABAA-, NMDA-, AMPA-, and kainate-evoked current responses recorded from cultured rat hippocampal neurones, using the whole cell patch clamp technique. GABA-evoked currents were reversibly inhibited by bicuculline (3 μM) and ciprofloxacin (100 μM) to 11 ± 5 and 38 ± 7% of control, respectively. BPAA (100 μM) had little affect on the GABA current (the response was 82 ± 4% of control) but enhanced the inhibitory potency of ciprofloxacin by approx. 3000-fold. The antagonist effects of ciprofloxacin (30 μM) and ciprofloxacin (0.03 μM) together with BPAA (100 μ M) on the GABA-evoked current were not voltage-dependent. Whole cell currents evoked by NMDA, AMPA or kainate were little influenced by ciprofloxacin (100 μM), BPAA (100 μM), or ciprofloxacin plus BPAA (both at 100 μM); the responses being ≥90% of control in all cases. These data suggest that the proconvulsant effects of quinolones when combined with BPAA may be related to antagonism of central GABAA receptors but not to an interaction at ionotropic glutamate receptors.
AB - The neurotoxic effects of 4-quinolones alone and in combination with certain non-steroidal anti-inflammatory drugs (NSAIDs) may be related to an interaction at GABAA and/or ionotropic glutamate receptors. In the present study, the effects of the fluoroquinolone, ciprofloxacin, alone and in combination with the NSAID, biphenyl acetic acid (BPAA), were examined on GABAA-, NMDA-, AMPA-, and kainate-evoked current responses recorded from cultured rat hippocampal neurones, using the whole cell patch clamp technique. GABA-evoked currents were reversibly inhibited by bicuculline (3 μM) and ciprofloxacin (100 μM) to 11 ± 5 and 38 ± 7% of control, respectively. BPAA (100 μM) had little affect on the GABA current (the response was 82 ± 4% of control) but enhanced the inhibitory potency of ciprofloxacin by approx. 3000-fold. The antagonist effects of ciprofloxacin (30 μM) and ciprofloxacin (0.03 μM) together with BPAA (100 μ M) on the GABA-evoked current were not voltage-dependent. Whole cell currents evoked by NMDA, AMPA or kainate were little influenced by ciprofloxacin (100 μM), BPAA (100 μM), or ciprofloxacin plus BPAA (both at 100 μM); the responses being ≥90% of control in all cases. These data suggest that the proconvulsant effects of quinolones when combined with BPAA may be related to antagonism of central GABAA receptors but not to an interaction at ionotropic glutamate receptors.
KW - biphenyl acetic acid
KW - ciprofloxacin
KW - GABA receptor
KW - hippocampal neurones
KW - ionotropic glutamate receptors
KW - Quinolones
UR - http://www.scopus.com/inward/record.url?scp=0029587539&partnerID=8YFLogxK
U2 - 10.1016/0028-3908(95)00106-9
DO - 10.1016/0028-3908(95)00106-9
M3 - Article
C2 - 8788959
AN - SCOPUS:0029587539
VL - 34
SP - 1615
EP - 1624
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 12
ER -