Effect of norfloxacin, a new quinolone, on GABA modulation of TRH-induced TSH release from perifused rat pituitaries.
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 mumol/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.
Roussel
J P
JP
Laboratoire de Neuroendocrinologie, Université de Montepellier II, France.
Tapia-Arancibia
L
L
Jourdan
J
J
Astier
H
H
D000818:Animals; D007539:Isonicotinic Acids / Q000008:administration & dosage; D008297:Male; D009643:Norfloxacin / Q000494:pharmacology*; D010477:Perfusion; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage
D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D009643:Norfloxacin; C015300:isoguvacine