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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that serotonin plays an important role in learning and memory processes in animals. The present study examined the effect of the 5-HT3 receptor antagonist, granisetron (BRL 43694), on acquisition, retention and retrieval of a passive avoidance response in mice. Granisetron (1 and 10 micrograms/kg) administered 30 min before presentation of footshock increased the step-down latency when tested 24 h after footshock. The acquisition process was not affected by a dose of 100 micrograms/kg. Granisetron (10 and 100 micrograms/kg) produced a significant increase in latency to step out of the safety zone, when administered immediately after or 23.5 h after footshock. However, at 1 microgram/kg, granisetron had no effect. These results confirm the important role played by 5-HT in the process of learning and memory, and also suggest that memory enhancement may be possible with non-cholinergic treatments.
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PMID:Memory enhancing effects of granisetron (BRL 43694) in a passive avoidance task. 166 86

Both radiotherapy and chemotherapy for cancer are capable of causing severe nausea and vomiting, which formerly often interfered with the patient's compliance to treatment. The basic pathway and pharmacological mechanisms involved in this are still poorly understood. The recent discovery, however, that 5-HT3 receptor antagonists can prevent or greatly reduce chemotherapy-induced emesis led to a re-evaluation of the sequence of events occurring in the protective emetic reflex, which are reviewed in this paper. The vomiting centre co-ordinates the incoming and outgoing information, and is thought to be represented by complex interactions between different adjacent areas in the brainstem. Whether the main role in the emetic reflex arch is accomplished by either the central part (chemoreceptor trigger zone) or the peripheral part (gastro-intestinal tract) needs further confirmation A more important role, however, of the vagal nerve and the gastro-intestinal tract is generally accepted. The neurotransmitter serotonin (5-HT) appears to play a major role in chemotherapy-induced emesis via the 5-HT receptor. These indications could form the basis for further investigations into the involvement of other neurotransmitters, and the character of their interactions.
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PMID:Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear. 167

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

The vasodilator mechanism of the putative serotonin1A (5-HT) receptor agonists, urapidil, 5-methyl-urapidil, ipsapirone, flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated in constant-pressure perfused rat kidneys. The compounds (10(-12)-10(-7) mol bolus injection) neither enhanced basal flow nor evoked vasodilatation in kidneys preconstricted by 27 mM KCl, 1.5 mM BaCl2 or 10(-6) M prostaglandin (PG)F2 alpha, but evoked a dose-dependent, reversible and spiroxatrine-resistant increase in vasodilatation of organs preconstricted by 6 x 10(-7) M noradrenaline. 5-Carboxamidotryptamine and sumatriptan did not reverse the vasoconstriction induced by all stimuli or that induced by noradrenaline in the presence of 5-HT2 plus 5-HT3 receptor blockade. No correlation for the vasorelaxant drugs was found between their -log ED50 in rat kidney and pKi values at 5-HT1A binding sites in pig cortex as determined in radioligand experiments. The relaxation in rat kidney induced by 5-HT1A receptor agonists and alpha 1A-adrenoceptor-selective antagonists (WB 4101 and (+)-niguldipine) was significantly correlated with pKi values at alpha 1A binding sites in rat cortex and the pA2 values derived from contraction studies for competitive antagonism at alpha 1-adrenoceptors in prostatic portions of the rat vas deferens, but differed from pKi values for alpha 1B binding sites in rat cortex. Thus, the vasodilator effect of the 5-HT1A receptor agonists urapidil, 5-methyl-urapidil, ipsapirone, flesinoxan and 8-OH-DPAT in the noradrenaline-perfused rat kidney appears to be mediated by their concomitant alpha 1A-adrenoceptor blockade. No evidence for a vasodilator effect mediated through 5-HT1A receptors was found under our experimental conditions.
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PMID:Vasodilatation elicited by 5-HT1A receptor agonists in constant-pressure-perfused rat kidney is mediated by blockade of alpha 1A-adrenoceptors. 168 54

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

The level of cyclic AMP in NCB-20 cells was increased by serotonin (5-HT), 5-methoxytryptamine and 2-methyl-5-HT with EC50 of 0.5 +/- 0.1, 1.0 +/- 0.1, 10 +/- 0.1 microM, respectively. The 5-HT-mediated increase of cyclic AMP content was completely blocked by metergoline but unaffected by 5-HT3 antagonists, ICS 205-930, MDL 72222, quipazine and 5-HT2 antagonist, ketanserin. Putative 5-HT1A agonists (8-OH-DPAT, ipsapirone, and buspirone) and 5-HT1B agonists (TFMPP and m-CPP) affected neither basal nor forskolin-dependent cyclic AMP accumulation. Receptor binding studies suggest that NCB-20 cells are devoid of 5-HT1A and 5-HT1B receptor sites. Application of 5-HT onto NCB-20 cells resulted in membrane depolarization by an evoked inward current which displayed rapid desensitization. 5-HT-mediated current had a reversal potential around 0 mV and was potently and reversibly inhibited by ICS 205-930. Our data suggest that in NCB-20 cells the 5-HT3 receptor is involved in the generation of inward currents, while the 5-HT receptor coupled to adenylate cyclase does not seem to correspond to any of the known receptor subtypes.
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PMID:Characterization of two distinct 5-HT receptors coupled to adenylate cyclase activation and ion current generation in NCB-20 cells. 168 72

5-HT3 receptor-mediated membrane currents were recorded from voltage-clamped clonal N1E-115 neuroblastoma cells. The inward current response to ionophoretically applied serotonin (5-HT) was reversibly antagonised by the 5-HT3 receptor antagonists GR 38032F and metoclopramide with IC50 values of 0.2 nM and 14 nM, respectively. Low concentrations of (+)-tubocurarine [+)-Tc) also blocked the response to 5-HT (IC50 = 0.8 nM), but other nicotinic cholinoceptor antagonists (gallamine, vecuronium and trimetaphan) were ineffective when applied at a relatively high concentration (1 microM). Blockade by (+)-Tc was neither voltage- nor use-dependent, suggesting that (+)-Tc does not block 5-HT-activated ion channels in N1E-115 cells.
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PMID:Antagonism of 5-HT3 receptor mediated currents in murine N1E-115 neuroblastoma cells by (+)-tubocurarine. 169 68

1. The effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists on the behavioural hyperactivity response which results from injection of the neurokinin receptor agonist [pGlu5, MePhe8, Sar9]-substance P (5-11) (DiMe-C7) into the ventral tegmental area (VTA) of the rat midbrain have been determined. 2. Subcutaneous administration of ondansetron (GR38032) (0.001-0.3 mg kg-1), GR65630 (0.01 mg kg-1), ICS 205-930 (0.1 mg kg-1) and MDL 72222 (0.1 mg kg-1), inhibited the DiMe-C7-induced hyperactivity response. 3. The effects of ondansetron on DiMe-C7-induced changes in dopamine and 5-HT metabolism in discrete areas of rat forebrain were studied in order to investigate further the possible mechanism of action of 5-HT3 antagonists in modifying mesolimbic dopaminergic systems. 4. Intra-VTA administration of DiMe-C7 increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens, olfactory tubercules and right amygdala, indicating increased mesolimbic dopamine metabolism. DOPAC levels were not significantly increased in the frontal cortex, left amygdala or striatum. Dopamine levels were not altered in any of these brain areas. DiMe-C7 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels in the amygdala but this was only statistically significant in the right amygdala. 5-HT levels were not changed significantly by DiMe-C7 treatment. 5. In control rats, pretreatment with ondansetron (0.1 mg kg-1) had no effect on the levels of dopamine, 5-HT or their metabolites, but in rats given DiMe-C7, ondansetron significantly inhibited the increase in DOPAC levels in the nucleus accumbens. 6. These results are in agreement with the proposed facilitatory role of 5-HT3 receptor activation on mesolimbic dopaminergic transmission, and suggest that 5-HT3 antagonists may have important therapeutic indications for the treatment of CNS disorders in which mesolimbic dopamine systems are perturbed.
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PMID:Effect of 5-HT3 receptor antagonists on responses to selective activation of mesolimbic dopaminergic pathways in the rat. 169 72

The effect of acute ethanol (EtOH) exposure on 5-HT3 receptor-mediated ion current was examined in whole-cell patch-clamp recordings from NCB-20 neuroblastoma cells. The physiologic and pharmacologic properties of 5-HT-activated ion current in NCB-20 cells indicated that it was mediated by 5-HT3 receptors. EtOH potentiated 5-HT3 receptor-mediated current in a concentration-dependent manner at concentrations (25-100 mM) which are achieved during EtOH intoxication in vivo.
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PMID:Ethanol potentiation of 5-HT3 receptor-mediated ion current in NCB-20 neuroblastoma cells. 171 59

Recent studies indicate that ethanol (EtOH) potentiates ion current through the channel associated with the 5-hydroxytryptamine3 (5-HT3)-type serotonin receptor. The present study was designed to determine 1) whether such potentiation occurs in adult mammalian neurons expressing 5-HT3 receptors; 2) whether potentiation is selective for the 5-HT3 receptor, relative to other ligand-gated ion channels; and 3) possible mechanisms by which EtOH potentiates this response. EtOH potentiated 5-HT3 receptor-mediated ion current in freshly isolated nodose ganglion neurons at concentrations similar to those previously reported to be effective in neuroblastoma cells (25-100 mM). Current was blocked by the selective 5-HT3 antagonist ICS 205-930 even in the presence of EtOH, and current activated by a 5-HT3 agonist (2-methyl-5-HT) was potentiated by EtOH. Thus, EtOH appears to produce potentiation via an alteration in the function of 5-HT3 receptors and not through an independent effect. gamma-Aminobutyric acidA receptor-mediated Cl- current was not potentiated by EtOH in neurons in which potentiation of responses to 5-HT was observed. Methanol potentiated 5-HT3 receptor-mediated current with a potency lower than that of EtOH. Potentiation by EtOH decreased with increasing 5-HT concentration. In addition, EtOH increased the decay rate of current. EtOH did not alter the reversal potential of the 5-HT3 receptor-mediated current. These observations indicate that intoxicating concentrations of EtOH selectively potentiate 5-HT3 receptor-mediated responses by increasing the apparent potency of 5-HT for activating ion current.
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PMID:Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. 171 16


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