Inhibitory effect of taurine on 4-aminopyridine-stimulated release of labelled dopamine from striatal synaptosomes.

4-Aminopyridine (4-AP) stimulated the release of [3H]dopamine from striatal synaptosomes in the rat. At a concentration of 200 microM, 4-aminopyridine increased the spontaneous efflux of dopamine by 170%. The effect of 4-aminopyridine was calcium-dependent, being abolished when calcium was omitted from the incubation medium. Taurine, at a concentration of 25 mM, decreased the stimulatory effect of 4-aminopyridine from 170 to 49%, in the presence of 2.5 mM calcium. When the concentration of calcium in the superfusion medium was reduced to 0.1 mM, taurine had a complete inhibitory effect on the release of [3H]dopamine stimulated by 4-aminopyridine. The effect of taurine was dose-dependent. Glycine had no effect on the release of [3H]dopamine stimulated by 4-aminopyridine, either in the presence of absence of calcium, whereas gamma-aminobutyric acid (GABA) showed a slight inhibitory effect in both conditions. The results suggest that taurine antagonizes the release of [3H]dopamine induced by 4-aminopyridine through an effect mediated by calcium.

Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine.

The susceptibility of rats made deficient of taurine by treatment with guanidinoethane sulfonate (GES), to seizures induced by 4-aminopyridine was examined. Guanidinoethane sulfonate, at a concentration of 1% was administered to pregnant rats, in the drinking water 2-3 days prior to delivery and the treatment was continued during nursing. Pups were weaned to the same treatment until 6 weeks of age. This treatment decreased levels of taurine in the cerebral cortex by 70%. 4-Aminopyridine was injected intraperitoneally at doses ranging from 4-7 mg/kg. Taurine-deficient rats showed a greater susceptibility to seizures, as demonstrated by a lowered latency for clonic seizures, an increased incidence of tonic seizures and a higher postseizure mortality. These results suggest an involvement of endogenous taurine in nervous excitability.

Effect of taurine on seizures induced by 4-aminopyridine.

The effect of intraperitoneally injected taurine against the convulsive activity induced by 4-aminopyridine (4-AP) was studied in 12- to 15-day-old mice. At a dose of 2.6 mg/kg, taurine increased the latency of clonic seizures from 7 to 20 minutes, reduced the incidence of tonic seizures from 92% to 30% and the postconvulsive mortality from 80% to 31%. The injection of EDTA prior to the administration of taurine prevented the protective effects of the amino acid. GABA and glycine at the same doses did not protect against 4-AP-induced seizures. 4-AP caused a small increase (19%) in 45Ca accumulation by mice brain synaptosomes incubated in a Krebs-HEPES medium containing low CaCl2 (0.1 mM) and also slightly potentiated the veratrine and potassium-induced increase in calcium accumulation. 4-AP at concentrations of 1-2 mM caused a marked increase (100%-500%) of 45 Ca accumulation by synaptosomes incubated in a Krebs-bicarbonate medium containing 2.5 mM CaCl2. This increase was completely antagonized by taurine but not by GABA of glycine. The present observations suggest that the anticonvulsant effect of taurine might be mediated by 4-AP-calcium-taurine interactions.

Antagonistic effects of taurine and 4-aminopyridine on guinea pig ileum.

The effects of 4-aminopyridine (4-AP) and of taurine on the guinea pig ileum were examined. Four-AP increases the basal activity from 1.3 to 6.45 cm2/min. This effect is atropine-sensitive and calcium-dependent. Taurine counteracts the effects of 4-AP on muscle contracture in a concentration-dependent manner. In muscles preincubated with 20 mM taurine, the effect of 4-AP decreased about 65%. Taurine added at the time of maximal effect of 4-AP reduced the muscle contracture induced by the drug to the basal levels. Glycine and beta-alanine did not influence the contracture induced by 4-AP, whereas 25 mM gamma-aminobutyric acid (GABA) reduced it by 30%. Taurine reduced the basal muscle activity by 50% but did not affect the contracture induced by exogenously applied acetylcholine.