抄録
5-hydroxytryptamine (5-HT; serotonin) inhibits transmitter release via activating GTP binding (G) proteins, but the target of this effect in the nerve terminal is not determined. We addressed this question at the calyx of Held synapse in brainstem slices of developing rats. In 5-day-old rats bath-application of 5-HT (10 μM) attenuated the amplitude of evoked EPSCs and facilitated paired-pulse ratio, whereas 5-HT had no effect on the amplitude of spontaneous miniature EPSCs. The 5-HT1B receptor agonist CP93129 mimicked the inhibitory effect of 5-HT, but the 5-HT1A agonist 8-OHDPAT had no effect. 5-HT1B receptor antagonist NAS-181 blocked the inhibitory effect of 5-HT. These results suggest that 5-HT activate 5-HT1B receptors in the nerve terminal, thereby inhibiting transmitter release. In whole-cell recordings from calyceal nereve terminals, 5-HT attenuated voltage-gated Ca2+ currents, but had no effect on voltage-gated K+ currents. Upon repetitive application 5-HT showed tachyphylaxis with its effect on both EPSCs and presynaptic Ca2+ currents becoming weaker in the second application. Surprisingly 10 mM BAPTA loaded into the nerve terminal abolished the tachyphylaxis. The presynaptic inhibitory effect of 5-HT was robust at postnatal day 5, but became weaker as animals matured. We conclude that 5-HT1B receptors can mediate presynaptic inhibition of transmitter release in immature calyceal terminals via inhibiting voltage-gated Ca2+ channels. Upon repetitive activation 5-HT1B receptors may be internalized or desensitized by a Ca2+-dependent mechanism. [J Physiol Sci. 2006;56 Suppl:S86]
