Effect of norfloxacin, a new quinolone, on GABA modulation of TRH-induced TSH release from perifused rat pituitaries

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Abstract
The effect of the quinolone norfloxacin, a new antibacterial agent that is thought to induce convulsions in patients by inhibiting the binding of GABA, was tested on the two kinds of GABA A modulation of fTRH-induced TSH release from perifused rat pituitaries. Norfloxacin (50 .mu.mol/l) was found to reverse the inhibitory effect of GABA (100 nmol/l) on the TSH release induced by TRH (10 nmol/l). The ratio of induced over spontaneous release was 0.79 .+-. 0.05 in the presence of GABA, and 2.32 .+-. 0.18 when norfloxacin was added 15 min before GABA vs 2.59 .+-. 0.09 in the control response to TRH. Norfloxacin was also able to reverse the potentiating effect of GABA (10 nmol/l): the TSH response was 6.56 .+-. 0.94 in the presence of GABA alone vs 2.92 .+-. 0.35 with norfloxacin plus GABA. Norfloxacin was also able to reverse the potentiation induced by isoguvacine, a specific GABA A agonist (6.15 .+-. 1.14 in the presence of isoguvacine vs 2.99 .+-. 0.54 with norfloxacin plus isoguvacine). Our results suggest that norfloxacin may antagonize the effect of GABA via the two classes of GABA A receptor sites which differ in affinity and are responsible for the dual effect of GABA on the TRH-induced TSH secretion.