Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of serotonin on inhibitory synaptic transmission was examined in forty-one CA1 pyramidal neurones using intracellular voltage recordings in vitro. 2. Serotonin (20-50 microM) increased the synaptic noise of most (85%) neurones loaded with chloride (n = 33). The duration of this effect was enhanced with increasing concentrations of serotonin and was fully reversible within 5 min. When serotonin was applied at short intervals (less than 10 min), fading of the response was observed. 3. The effect of serotonin on synaptic noise persisted in the presence of the glutamate NMDA and non-NMDA antagonists, APV (100 microM) and CNQX (10 microM), but it was blocked (n = 5) by a GABAA antagonist, bicuculline (10 microM). 4. The increase in inhibitory synaptic events resulted from an enhanced frequency of unitary IPSPs from 4.6 +/- 3.8 Hz in control to 17.2 +/- 12.5 Hz (n = 5) in serotonin, especially of large events. Serotonin caused no change in the amplitude and frequency of miniature synaptic events recorded in the presence of TTX (n = 5). The mean amplitude of unitary inhibitory postsynaptic potentials (IPSPs) increased from 1.37 +/- 0.35 mV in control to 3.67 +/- 1.38 mV in serotonin. The coefficient of variation of unitary IPSPs increased from 0.40 +/- 0.11 in control to 0.74 +/- 0.23 in serotonin when quantal size appeared unchanged. 5. The 5-HT3 agonist 2-methyl-serotonin (52 microM, n = 4) partially mimicked the effect of serotonin, increasing the inhibitory noise without affecting the pyramidal neurone conductance. The serotonin-induced facilitation of unitary IPSPs was blocked by the 5-HT3 antagonists ICS 205-930 (1-90 nM, n = 3) and metoclopramide (30 microM, n = 1). 6. These results suggest that serotonin directly excites GABAergic interneurones acting on a 5-HT3 receptor and consequently increasing the frequency of inhibitory synaptic events recorded in CA1 pyramidal cells.
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PMID:Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro. 168 46

Intra- and extracellular recordings from the in vitro rat hippocampal slice preparation have been used to investigate the influence of serotoninergic, adrenergic and cholinergic receptor antagonists on the excitability of CA1 pyramidal neurones. The serotonin receptor antagonist 4-amino-N-(1-azabicyclo[2.2.2]oct-3yl)-5-chloro-2- methoxybenzamide(E)-2-butenedioate (zacopride, 100 microM) produced multiple population spikes on the orthodromically evoked field potential, in contrast to the lack of effect of another serotonin antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222, 30 microM), as well as the cholinergic antagonists atropine (10 microM) and hexamethonium (100 microM) and the noradrenergic antagonist atenolol (10 microM). Monosynaptic inhibitory postsynaptic potentials (IPSPs) recorded in the presence of the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and ketamine (50 microM) were recorded from CA1 pyramidal neurones. Zacopride (100 microM) and MDL 72222 (30 microM) both reduced the isolated IPSP to 54 +/- 9% (n = 8) and 78 +/- 4% (n = 3), respectively. Neither of the cholinergic antagonists had any effect, while atenolol reduced the IPSP to 87 +/- 3% (n = 7) of the control IPSP. We propose that the difference in action of zacopride and MDL 72222 on the field potentials is due to zacopride activating postsynaptic 5HT4 receptors on the pyramidal neurone, thereby reducing a Ca(2+)-activated K(+)-conductance. This, in combination with a 5HT3 receptor-mediated reduction in gamma-aminobutyric acid (GABA)-ergic inhibition, leads to an increase in pyramidal cell excitability evident as epileptic field potentials.
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PMID:Serotoninergic modulation of excitability in area CA1 of the in vitro rat hippocampus. 857

Whole-cell voltage-clamp recordings were performed to investigate the serotonergic modulation of neurotransmitter release onto rat area postrema neurons in vitro. The bath application of serotonin (5-HT; 50 microM) or phenylbiguanide (PBA; 50 microM), a potent 5-HT3 receptor agonist, increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) or miniature EPSCs (mEPSCs) in 35 of 83 neurons (42%). These increases occurred in all electrophysiological cell classes. No cells exhibited a decrease in EPSC frequency. The majority of responding cells showed no inward currents during the application of serotonergic agonists (n = 34/35). However, the amplitude of mEPSCs was increased in 11/11 cells with 5-HT or 3/11 cells with PBA. ICS-205,930, a potent 5-HT3 receptor antagonist, markedly suppressed the 5-HT-induced facilitation of sEPSCs (n = 5) or mEPSCs (n = 5). An increase in the frequency of mEPSCs after PBA exposure was found, even with media containing Cd2+ (50 microM) or zero Ca2+. mEPSCs and evoked EPSCs were completely blocked in media containing the non-NMDA ionotropic receptor antagonist, CNQX (10 microM), indicating that EPSCs were glutamate events. These results suggest that glutamate release is increased in the area postrema by presynaptic 5-HT3 receptor activation. Furthermore, we present evidence that 5-HT3 receptor activation may be able to directly release glutamate from terminals, bypassing a requirement for voltage-dependent calcium entry into terminals. Such a mechanism may contribute to the chemosensitive function of area postrema neurons.
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PMID:Activation of presynaptic 5-HT3 receptors facilitates glutamatergic synaptic inputs to area postrema neurons in rat brain slices. 1560 21

Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related excitatory inputs under normal conditions. However, excitatory purinergic and serotonergic pathways are recruited during inspiratory activity after episodes of hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to dramatically change cardiorespiratory responses and decrease the ability to resuscitate from H/H. This study tested whether PNN exposure alters excitatory neurotransmission to CVNs in the nucleus ambiguus during and after H/H. Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded in CVNs from rats that were exposed to nicotine (6 mg x kg(-1) x d(-1)) throughout the prenatal period. In contrast to unexposed animals, in PNN animals H/H recruited excitatory neurotransmission to CVNs during inspiratory-related activity that was blocked by the alpha3beta4 nicotinic acetylcholine receptor (nAChR) blocker alpha-conotoxin AuIB (alpha-CTX AuIB, 100 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 microM) and d(-)-2-amino-5-phosphonopentanoic acid (AP5, 50 microM), selective AMPA/kainate and N-methyl-d-aspartate receptor blockers, respectively. Following H/H, there was a significant increase in inspiratory-related excitatory postsynaptic currents that were unaltered by alpha-CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (100 microM), a purinergic receptor blocker and CNQX and AP5. The results from this study demonstrate that with PNN exposure, an excitatory neurotransmission to CVNs is recruited during H/H that is glutamatergic and dependent on activation of alpha3beta4-containing nAChRs. Furthermore, exposure to PNN abolishes a serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced by recruitment of a glutamatergic pathway to CVNs post H/H.
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PMID:Abolishment of serotonergic neurotransmission to cardiac vagal neurons during and after hypoxia and hypercapnia with prenatal nicotine exposure. 1909 27