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

The effect of the novel agonist, 1-(m-chlorophenyl)-biguanide (mCPBG) was examined on 5-HT3 receptors in NG108-15 mouse neuroblastoma x rat glioma hybrid cells, using whole-cell voltage-clamp and radioligand binding on intact cells. Electrophysiological studies showed that mCPBG is a partial agonist, with an EC50 of 3.1 microM. Displacement of the selective 5-HT3 receptor antagonist [3H]GR65630 by mCPBG revealed a Ki of 14.2 nM. The study suggests that mCPBG may have a high affinity for desensitized 5-HT3 receptors and also revealed some differences between 5-HT3 receptors in NG108-15 and N1E-115 cells.
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PMID:5-HT3 receptors in NG108-15 neuroblastoma x glioma cells: effect of the novel agonist 1-(m-chlorophenyl)-biguanide. 140 96

1-(m-Chlorophenyl)-biguanide (mCPBG) was examined and compared with three 5-HT3 receptor agonists in three 5-HT3 receptor models. mCPBG inhibited [3H]GR67330 binding to 5-HT3 receptors with high affinity (IC50 1.5 nM). mCPBG depolarized the rat vagus nerve with an EC50 one tenth of that for 5-HT (0.05 vs. 0.46 microM); the maximum depolarization was approximately half that for 5-HT. The mCPBG depolarization was potently blocked by the selective 5-HT3 antagonist, ondansetron (pKB 8.6 +/- 0.1). In anaesthetised cats, mCPBG potently evoked the Bezold-Jarisch reflex which was blocked by low doses of ondansetron (10 micrograms/kg i.v.). It is concluded that mCPBG is a potent, high affinity 5-HT3 receptor agonist.
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PMID:1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist. 214 22

This experiment examined alterations in the ability of the highly selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG), to induce dopamine (DA) overflow in caudate brain slices obtained from rats withdrawn from continuous or intermittent cocaine administration. Rats were pretreated with 40 mg/kg per day cocaine for 14 days by either subcutaneous injections or osmotic minipumps, and then withdrawn from this regimen for 7 days. Caudate brain slices were obtained, and perfused with artificial cerebrospinal fluid. Following an equilibration period, the slices were then perfused with 25, 50, or 100 microM mCPBG. The samples were assayed for DA content by HPLC with electrochemical detection. The results indicated that the pretreatment with intermittent cocaine did not consistently alter the ability of mCPBG to induce DA overflow, although there was a reduction in the amount of DA released by the highest concentration of mCPBG. In contrast, pretreatment with continuous cocaine administration consistently and significantly attenuated the ability of mCPBG to induce DA overflow. The DA overflow induced by mCPBG was partially dependent on extracellular Ca2+ in the perfusion medium for the saline control and intermittent administration subjects: elimination of Ca2+ from the medium significantly reduced, but did not eliminate, DA overflow for these two groups. In contrast, elimination of Ca2+ from the perfusion medium had a significant enhancing effect on mCPBG-induced DA overflow in the continuous administration rats. These results suggest that distinct temporal patterns of cocaine administration differentially alter the ability of a 5-HT3 agonist to increase extracellular DA levels, and that this effect may be related to an impairment of Ca(2+)-dependent release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT3 agonist-induced dopamine overflow during withdrawal from continuous or intermittent cocaine administration. 760 48

We have used single-cell imaging of fura-2-loaded cells to examine the Ca2+ signals evoked by activation of 5-hydroxytryptamine type 3 (5-HT3) receptors in undifferentiated N1E-115 neuroblastoma cells and in human embryonic kidney (HEK) 293 cells transfected with either of the two cloned 5-HT3 receptor subunits. The selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) caused a concentration-dependent increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) in N1E-115 cells and in HEK 293 cells transfected with either the 5-HT3 A subunit or the 5-HT3 As subunit. In each case, the [Ca2+]i rise was steeply dependent on the mCPBG concentration (nH = 2-4) and abolished by removal of extracellular Ca2+ or addition of ondansetron. Pretreatment of N1E-115 cells with thapsigargin, caffeine, and ryanodine to deplete intracellular Ca2+ stores had no effect on the mCPBG-evoked Ca2+ signals, indicating that they result entirely from stimulated Ca2+ entry. The steep concentration-effect curves therefore are not a consequence of amplification of Ca2+ influx by Ca(2+)-induced Ca2+ release from intracellular stores and probably reflect cooperative activation of 5-HT3 receptors by mCPBG. Depolarization of transfected HEK 293 cells with medium containing increased K+ concentrations invariably failed to evoke an increase in [Ca2+]i, confirming the absence of voltage-gated Ca2+ channels and indicating that the mCPBG-evoked rise in [Ca2+]i results from Ca2+ permeation of 5-HT3 receptors. However, in N1E-115 cells and transfected HEK 293 cells, both extracellular Na+ and K+ substantially inhibited the Ca2+ influx evoked by activation of 5-HT3 receptors, possibly by inhibition of agonist binding or by competition with Ca2+ for permeation of the channel. We conclude that 5-HT3 receptors are Ca2+ permeant, that the Ca2+ influx is sufficient to generate a significant rise in [Ca2+]i, and that, because the A and As subunits behave similarly, conflicting electrophysiological analyses of Ca2+ currents cannot be explained by differences between these two subunits.
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PMID:Ca2+ permeability of cloned and native 5-hydroxytryptamine type 3 receptors. 780 32

We analyzed the facilitatory effect of the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) on the electrically evoked noradrenaline release in superfused mouse brain tissue. In addition, we determined the affinities of mCPBG and two other 5-HT receptor ligands, namely 2-methyl-5-hydroxytryptamine (2-methyl-5-HT; also a 5-HT3 receptor agonist) and 5-carboxamidotryptamine (5-CT; a 5-HT1 receptor agonist) for alpha 2 binding sites. The latter two 5-HT receptor agonists were included because of the claimed involvement of alpha 2-adrenoceptors in their effects on noradrenaline release. In superfusion experiments on mouse brain cortex slices preincubated with 3H-noradrenaline, tritium overflow evoked by 2-min periods of electrical field stimulation (3 Hz) was facilitated by mCPBG and, in addition, by rauwolscine (alpha 2-adrenoceptor antagonist) and tetraethylammonium (K+ channel blocker) (which were examined for comparison). The effect of mCPBG was not affected by the 5-HT3 receptor antagonist tropisetron or by desipramine but was abolished by rauwolscine. In slices superfused with medium containing desipramine, the concentration-response curve of unlabelled noradrenaline for its inhibitory effect on the electrically (0.3 Hz) evoked overflow was shifted to the right by mCPBG and rauwolscine (apparent pA2 5.35 and 7.88, respectively). In another series of superfusion experiments, 4 electrical pulses, administered at 100 Hz, were used to evoke tritium overflow. Tritium overflow evoked by this stimulation procedure (under which an endogenous tone of noradrenaline does not develop) was not affected by mCPBG and rauwolscine but still increased by tetraethylammonium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide facilitates noradrenaline release by blockade of alpha 2-adrenoceptors in the mouse brain cortex. 790 22

The effects of 5-HT3-receptor-related agents on long-term potentiation (LTP) in the mossy fiber-CA3 system were studied in guinea pig hippocampal slices. 5-HT3 receptor agonists, 1-(m-chlorophenyl)-biguanide (mCPBG) and 2-methyl serotonin (2-Me-5-HT) significantly attenuated the magnitude of LTP of the population spike at 0.3-1 microM and at 10 microM respectively. At these doses neither of these drugs did affect the amplitude of the population spike (PSA) evoked by test stimuli in the absence of tetanic stimulation. The attenuating effect of mCPBG on LTP was reversed by the GABAA receptor antagonist bicuculline. On the other hand, 5-HT3 receptor antagonists ondansetron and granisetron significantly augmented the magnitude of LTP at 1-3 microM and at 0.1-0.3 microM, respectively, without changes in PSA before tetanus. The augmenting effect of granisetron on LTP was partially but significantly reversed by the muscarinic receptor antagonist atropine. These findings suggest that the induction of the LTP in the mossy fiber-CA3 system is inhibited by an activation of 5-HT3 receptors through the facilitation of GABAergic neurons (GABAA receptors) and the inhibition of cholinergic neurons (muscarinic receptors).
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PMID:Inhibitory influence via 5-HT3 receptors on the induction of LTP in mossy fiber-CA3 system of guinea-pig hippocampal slices. 819 Mar 70

The binding of the tritiated derivative of the 5-HT3 receptor agonist meta-chlorophenylbiguanide ([3H]mCPBG) to rat cortical homogenates and whole rat brain sections was assessed in an attempt to further investigate the binding of agonists to the 5-HT3 receptor. In crude homogenates of rat cortex, no reproducible specific [3H]mCPBG (1.0 nM) binding (defined by either 10 microM granisetron, 100 microM 5-HT or 100 nM 'cold' mCPBG) was detected. Using autoradiographic techniques, in rat hindbrain sections, [3H]mCPBG (1.0 nM) labelled a differential distribution of specific binding sites (defined by the inclusion of granisetron, 1.0 microM). Specific binding was only detected within the dorsal vagal complex (nucleus tractus solitarius, area postrema and dorsal motor nucleus of the vagus nerve). An identical distribution of specific binding was detected in adjacent sections incubated with the selective 5-HT3 receptor radioligand, [3H](S)-zacopride (0.5 nM; non-specific binding defined by the inclusion of granisetron, 1.0 microM). No reproducible specific [3H]mCPBG (1.0 nM) binding (defined by the inclusion of granisetron, 1.0 microM) was detected within the rat forebrain. In contrast, [3H](S)-zacopride (0.5 nM) labelled specific sites (defined by the inclusion of granisetron, 1.0 microM) in some limbic brain structures (e.g. cerebral cortex, hippocampus, amygdala). These studies indicate that [3H]mCPBG labels the 5-HT3 receptor in rat brain tissue. However, the relatively high level of non-specific binding associated with this radioligand appears to mask the specific binding in regions which do not express relatively high densities of the 5-HT3 receptor.
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PMID:Labelling of 5-HT3 receptor recognition sites in the rat brain using the agonist radioligand [3H]meta-chlorophenylbiguanide. 825 20

The effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide, were compared with those of the 5-HT3 receptor antagonist, MDL 72222, in rats implanted with electrodes for chronic sleep recordings. m-Chlorophenylbiguanide (12.5-50.0 micrograms) injected into the left lateral ventricle increased wakefulness and rapid eye movement (REM) sleep latency, whereas slow wave sleep, REM sleep and the number of REM periods were reduced. MDL 72222 (0.1-1.0 mg/kg, s.c.) induced a delayed and dose-dependent increase of slow wave sleep. Pretreatment with MDL 72222 (0.1-0.5 mg/kg) prevented the effects of m-chlorophenylbiguanide (50 micrograms) on wakefulness and sleep. It is suggested that the increase of wakefulness after 5-HT3 receptor activation could be related to the release of endogenous serotonin and dopamine.
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PMID:The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat. 828 12

Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of serotonin receptor. The antiemetic effects of LY228729 [(-)-4-(dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)indole-6- carboxamide], a 5-HT1A receptor agonist, were tested and compared to the antiemetic effects of the 5-HT3 receptor antagonists ondansetron, tropisetron, and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3 antagonists in species other than the pigeon. In the pigeon, LY228729 totally abolished vomiting induced by fully emetic doses of cisplatin (10 mg/kg), ipecac (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide (1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-related manner and was partially effective in attenuating cisplatin-induced emesis. Ondansetron and tropisetron were partially effective in blocking emetine- and mCPBG-induced vomiting. Ondansetron exhibited an intrinsic emetic response that could not be blocked by MDL 7222, but which was eliminated by LY228729. It was concluded that 5-HT1A agonists are more effective in the pigeon than are 5-HT3 antagonists against these types of emetic stimuli. These results broaden the range of emetic stimuli that are blocked by 5-HT1A agonists in the pigeon.
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PMID:Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon. 854 76

Recent studies have suggested that activity at different 5HT receptor subtypes in the spinal cord either inhibits or facilitates nociceptive processing in the spinal cord. The present study has examined the role of 5HT3 receptors in nociceptive processing in the dorsal horn of the rat spinal cord. Using both behavioural and electrophysiological studies, 5HT3 ligands have been applied by a common route (i.e. intrathecal microinjection). In addition, only noxious heat has been used as a form of stimulation. Intrathecal injection of mCPBG (0.02-0.2 nmol) increased the responsiveness of dorsal horn neurones to noxious stimulation. In contrast, two 5HT3 antagonists (ICS 205-930 (0.015-0.15 nmol) and GR 380032F (ondansetron 34 nmol)) reduced nociceptive responses. Using doses which influenced nociceptive neuronal responses no significant change in TFL was recorded. These findings suggest that activation at 5HT3 receptor facilitates nociceptive responses of some dorsal horn neurones; these results are discussed in relation to earlier reports concerning alternative effects.
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PMID:The role of 5HT3 in nociceptive processing in the rat spinal cord: results from behavioural and electrophysiological studies. 873 5


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