title: 5-HT1B receptor-mediated presynaptic inhibition at the calyx of Held of immature rats.
abstract: 5-hydroxytryptamine (5-HT) inhibits transmitter release via activating GTP-binding proteins, but the target of 5-HT receptors in the nerve terminal is not determined. We addressed this question at the calyx of Held synapse in the brainstem slice of immature rats. Bath-application of 5-HT attenuated the amplitude of nerve-evoked excitatory postsynaptic currents (EPSCs) associated with an increase in the paired-pulse ratio, whereas it 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 (R)-(+)-8-hydroxy-DPAT (8-OHDPAT) had no effect. The 5-HT1B receptor antagonist NAS-181 blocked the inhibitory effect of 5-HT. These results suggest that 5-HT activated 5-HT1B receptors in calyceal nerve terminals, thereby inhibiting transmitter release. In direct whole-cell recordings from calyceal nerve terminals, 5-HT attenuated voltage-dependent Ca2+ currents, but had no effect on voltage-dependent K+ currents. When EPSCs were evoked by presynaptic Ca2+ currents during simultaneous pre- and postsynaptic recordings, the magnitude of the 5-HT-induced inhibition of Ca2+ currents fully explained that of EPSCs. Upon repetitive applications, 5-HT showed tachyphylaxis, with its effect on both EPSCs and presynaptic Ca2+ currents becoming weaker in the second application. 1,2-bis(o-aminophenoxy)ethane-N-N'-N'-N'-tetraacetic acid (BAPTA; 10 mm) loaded into the nerve terminal abolished this tachyphylaxis. The presynaptic inhibitory effect of 5-HT was prominent at postnatal day 5, but became weaker as animals matured. We conclude that activation of 5-HT1B receptors inhibits voltage-gated Ca2+ channels, thereby inhibiting transmitter release at immature calyceal nerve terminals, and that 5-HT1B receptors undergo Ca2+-dependent tachyphylaxis on repetitive activations.
authors.affiliation: Department of Neurophysiology, University of Tokyo Graduate School of Medicine, Tokyo 113-0033, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Mizutani
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hori
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology* / Q000254:growth & development; D002118:Calcium / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018755:GABA Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009025:Morpholines / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
chemical_list: C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; D001578:Benzopyrans; D018755:GABA Agonists; D009025:Morpholines; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one; D012701:Serotonin; D004533:Egtazic Acid; D001418:Baclofen; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium