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)

Until now, the only well documented, fast excitatory neurotransmitter in the brain has been glutamate. Although there is evidence for adenosine 5'-triphosphate (ATP) acting as a transmitter in the peripheral nervous system, suggestions for such a role in the central nervous system have so far not been supported by any direct evidence. Here we report the recording of evoked and miniature synaptic currents in the rat medial habenula. The fast rise time of the currents showed that they were mediated by a ligand-activated ion channel rather than a second messenger system, thus limiting the known transmitter candidates. Evidence was found for the presence on the cells of glutamate, gamma-aminobutyric acid, acetylcholine and ATP receptors, but not for 5-hydroxytryptamine (5HT3) or glycine receptors. The evoked currents were unaffected by blockers of glutamate, gamma-aminobutyric acid or acetylcholine receptors but were blocked by the ATP receptor-blocker, suramin and the desensitizing ATP receptor-agonist alpha,beta-methylene-ATP. Our evidence identifies for the first time synaptic currents in the brain, mediated directly by ATP receptors.
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PMID:ATP receptor-mediated synaptic currents in the central nervous system. 135 56

In this study, we have identified and characterized 5-HT3-like receptors in the rat medial prefrontal cortex (mPFc), an area with a moderate density of 5-HT3 binding sites, using the techniques of single unit recording and microiontophoresis. The microiontophoresis of the 5-HT3 receptor agonist 2-methylserotonin (2-Me-5HT), similar to the action of 5-HT, produced a current-dependent (10-80 nA) suppression of the firing rate of both spontaneously active and glutamate (GLU)-activated (quiescent) mPFc cells. Phenylbiguanide (PBG), another 5-HT3 receptor agonist, suppressed the firing rate of mPFc cells but was less effective compared to 2-Me-5HT. The continuous iontophoresis (10-20 min) of 1 M magnesium chloride markedly attenuated the suppressant effect produced by electrical stimulation of the ascending 5-HT pathway, but did not alter 2-Me-5HT's action, suggesting that the action of 2-Me-5HT is a direct one. The suppressant action of 2-Me-5HT on mPFc cells was blocked by a number of structurally diverse and selective 5-HT3 antagonists, with a rank order of effectiveness as follows: ICS 205930 = (+/-)-zacopride greater than granisetron = ondansetron = LY 278584 greater than MDL 72222. Furthermore, the intravenous administration of (+/-)-zacopride antagonized the action of 2-Me-5HT and PBG on mPFc cells. In contrast to the effects of the 5-HT3 receptors antagonists, other receptor antagonists such as metergoline (5-HT1A,1B,1C.2), (+/-)-pindolol (5-HT1A,1B, beta), SCH 23390 (5-HT1C.2, D1), l-sulpiride (D2) or SR 95103 (GABAA) failed to block 2-Me-5HT's action. These results combined suggest that 2-Me-5HT's suppressive action on mPFc cells is mediated directly by 5-HT3-like receptors.
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PMID:5-HT3-like receptors in the rat medial prefrontal cortex: an electrophysiological study. 167 70

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

Compared to traditional neuroleptics, most of the new antipsychotics are characterized by a low extrapyramidal side effect (EPS) liability and varying antipsychotic efficacy. This topic is reviewed for four principal classes of new, established, and potential antipsychotics: (1) Antipsychotics such as sulpiride and remoxipride that block a subgroup of dopamine (DA) D2/D3 receptors produce a relatively low level of side effects, including EPS, and have an antipsychotic effect equal to or slightly weaker than traditional neuroleptics. D1 antagonists demonstrate a low level of EPS in primates and may prove to be a valuable new type of antipsychotic drug. (2) Theoretically, partial D2 agonists have the advantage of producing few or no EPS and a specific beneficial effect in negative symptoms, but as yet the expectations have not been fulfilled. (3) Nondopamine drugs such as serotonin (5HT1) agonists, 5HT2 antagonists, 5HT3 antagonists, and gamma-amino-butyric-acid-A (GABA-A) benzodiazepine agonists have anxiolytic, antidepressant, antiaggressive, and maybe antiparkinsonian effects and may play an adjunctive role in the treatment of schizophrenia. 5HT3 antagonists (e.g., ondansetron), partial benzodiazepine agonists, and partial glutamate agonists may prove to be effective antipsychotics. (4) Antipsychotics such as clozapine and risperidone, which affect D2/D3 receptors as well as 5HT, alpha 1, and/or D1 receptors appear to have the most pronounced antipsychotic effect.
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PMID:New antipsychotics: classification, efficacy, and adverse effects. 171 8

1. The effects of microinjections (100 nl) into the dorsal motor vagal nucleus of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the 5-HT2 receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), the 5-HT3 receptor agonist phenylbiguanide (PBG), the alpha 2-adrenoceptor agonist clonidine and the excitatory amino acid glutamate on heart rate, blood pressure, tracheal pressure and phrenic nerve activity were investigated in atenolol-pretreated rats anaesthetized with sodium pentobarbitone. 2. Microinjections of glutamate (2.5 nmol) caused decreases in blood pressure, heart rate and phrenic nerve activity. In contrast, microinjections of 5-HT (1.2 nmol), 8-OH-DPAT (1.2 nmol) and flesinoxan (1.3 nmol) all caused a bradycardia but had no effect on blood pressure. In addition, 8-OH-DPAT and flesinoxan caused an increase in phrenic nerve activity. 3. Microinjections of DOI, PBG and clonidine had no significant effect on any of the variables recorded. None of the drugs used had any significant effect on tracheal pressure. 4. These results support the hypothesis that activation of 5-HT1A receptors causes excitation of cardiac vagal motoneurones and suggest that these receptors are also important in the control of central respiratory drive.
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PMID:Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. 179 13

The anti-hypertensive drug ifenprodil is known to interact potently with the alpha 1-adrenergic receptor as well as a number of other second messenger-linked receptors. In addition to these properties, ifenprodil has been shown to prevent glutamate-mediated excitotoxicity via non-competitive antagonism of NMDA receptors [Legendre and Westbrook (1991) Molec. Pharmac. 40: 289-298; Shalaby et al. (1992) J. Pharmac. Exp. Ther. 260: 925-932]. With these things in mind, we have begun to examine the specificity of ifenprodil for various ligand-gated ion channels using electrophysiological methods. While ifenprodil effectively inhibits NMDA-mediated currents in cortical neurons in culture, it does not interact with either kainate or GABA receptors. Surprisingly, ifenprodil also acts as a relatively potent antagonist of the 5-hydroxytryptamine3 (5-HT3) receptor in the NG108-15 neuroblastoma x glioma cell line. Furthermore, several aspects of ifenprodil action on the 5-HT3 receptor resemble its interaction with the NMDA receptor. Namely, inhibition of 5-HT3-mediated cation currents is readily reversible, has relatively slow onset, is non-competitive, and is not voltage dependent. Since most of the known 5-HT3 antagonists are competitive, it is possible that ifenprodil may define a unique modulatory site(s) on this neurotransmitter receptor.
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PMID:Ifenprodil inhibition of the 5-hydroxytryptamine3 receptor. 756 98

In vivo microdialysis was employed to measure release of endogenous L-glutamate (GLU) and L-aspartate (ASP) in the medial nucleus tractus solitarius of urethane anaesthetised rats. Basal extracellular levels of these amino acids were stable following a 90 min equilibration period (6.3 +/- 0.24 and 3.4 +/- 0.6 pmol/20 microliters sample of GLU and ASP, respectively). Basal levels of endogenous extracellular GLU and ASP were increased over 2-fold and 3-fold, respectively, following local administration of the selective 5-hydroxytryptamine (5-HT3) receptor agonist phenylbiguanide (300 microM). Intracerebral administration of the selective 5-HT3 receptor antagonist ondansetron (30 microM) blocked the effect of phenylbiguanide on GLU release whilst the effect on ASP was variable and complex. These data suggest that 5-HT3 receptor activation in the rat nucleus tractus solitarius can affect excitatory amino acid neurotransmission in this region of the medulla oblongata.
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PMID:5-Hydroxytryptamine3 receptor modulation of excitatory amino acid release in the rat nucleus tractus solitarius. 765 96

In previous studies, we showed that localized perfusion of the SCN region with serotonin (5-HT) or the non-selective serotonergic, quipazine, using the microdialysis technique significantly reduced the extracellular concentration of the excitatory amino acid (EAA), glutamate. The present investigation was undertaken to extend these findings by characterizing the effects of various classes of 5-HT receptor ligands on the extracellular glutamate concentration in the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly reduced the extracellular glutamate concentration in the SCN region from baseline levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist, TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and 5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively, had little effect on extracellular glutamate (both P > 0.1 vs. baseline). Systemic treatment with NAN-190 alone had little effect on extracellular glutamate, however, similar treatments with metergoline or the 5-HT2 receptor antagonist, ritanserin, induced significant increases extracellular glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear region assessed using in vivo brain microdialysis. 782 May 91

In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein.
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PMID:Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists. 786 72

In this study, we examined the interaction of 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex (mPFc) using the techniques of extracellular single unit recording and microiontophoresis. The iontophoresis of the selective 5-HT1A receptor agonist (+-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced a current-dependent suppression (2.5-20 nA) of the basal firing rate of spontaneously active mPFc cells. The iontophoretic (5-10 nA) and systemic administration (0.1-0.5 mg/kg, i.v.) of the 5-HT2A/5-HT2C receptor antagonist ritanserin and the selective 5-HT2A receptor antagonist MDL 28727 significantly potentiated and prolonged 8-OHDPAT's suppressant action. In addition, the systemic administration of another selective 5-HT2A antagonist MDL 100907, but not its less active enantiomer MDL 100009, also potentiated and prolonged 8-OHDPAT's action. The potentiating effect of the 5-HT2A receptor antagonists on the action of 8-OHDPAT is specific in that neither the iontophoresis of ritanserin nor MDL 28727 altered the suppressant action produced by the iontophoresis of the 5-HT3 receptor agonist 2-methylserotonin onto mPFc cells. Moreover, the suppressant action of 8-OHDPAT was not altered by the systemic administration of the selective 5-HT3 receptor antagonist granisetron (0.1-0.5 mg/kg, i.v.). On the other hand, the iontophoresis of a low current (0.5 nA) of the 5-HT2A,2C receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) potentiated the excitation induced by the iontophoresis of l-glutamate on quiescent mPFc cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrophysiological evidence for a functional interaction between 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex: an iontophoretic study. 797


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