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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. A comparative study of the whole-cell and single-channel properties of cloned and native mouse 5-hydroxytryptamine ionotropic receptors (5-HT3) was undertaken using mammalian cell lines expressing the cloned 5-HT3 receptor subunit A (5-HT3R-A), superior cervical ganglia (SCG) neurones and N1E-115 cells. 2. No pharmacological difference was found in the sensitivity to the agonists 5-HT and 2-methyl-5-HT, or to the antagonists d-tubocurare and 3-tropanyl-3,5-dichlorobenzoate (MDL-72222). 3. Current-voltage (I-V) relationships of whole-cell currents showed inward rectification in the three preparations. Rectification was stronger both in cells expressing the 5-HT3R-A subunit and in N1E-115 cells when compared with SCG neurones. 4. No clear openings could be resolved in 5-HT-activated currents in patches excised from cells expressing the 5-HT3R-A subunit or N1E-115 cells. Current fluctuation analysis of whole-cell and excised-patch records revealed a slope conductance of 0.4-0.6 pS in both preparations. Current-voltage relationships of these channels showed strong rectification that fully accounted for the whole-cell voltage dependence. 5. In contrast, single channels of about 10 pS were activated by 5-HT in patches excised from SCG neurones. The weak voltage dependence of their conductance did not account completely for the rectification of whole-cell currents. A lower unitary conductance (3.4 pS) was inferred from whole-cell noise analysis. 6. We conclude that the receptor expressed from the cloned cDNA is indistinguishable from the 5-HT3 receptor of N1E-115 cells, suggesting an identical structure for these two receptors. The higher conductance and different voltage dependence of the 5-HT3 receptor in SCG neurones might indicate the participation of an additional subunit in the structure of native ganglionic 5-HT3 receptors. Homo-oligomeric 5-HT3R-A channels may also be present as suggested by the lower conductance estimated by whole-cell noise analysis.
J Physiol 1994 Dec 01
PMID:Functional properties of a cloned 5-hydroxytryptamine ionotropic receptor subunit: comparison with native mouse receptors. 753 14

Previous studies have shown that local anesthetics block voltage-dependent Na+ channels and nicotinic acetylcholine receptors. The present study investigated the effect of the local anesthetic, procaine on another ligand-gated ion channel, the 5-HT3 receptor, in rat nodose ganglion neurons. Procaine (0.01-100 microM) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. The inhibition was fully reversible, concentration-dependent but not sensitive to changes in membrane potential. Concentration-response curves indicated that procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM. These observations suggest that one of the actions of procaine in nervous system is on 5-HT3 receptors.
Neuropharmacology 1994 Dec
PMID:Procaine impairs the function of 5-HT3 receptor-ion channel complex in rat sensory ganglion neurons. 753 14

Intracerebroventricular (i.c.v.) injection of highly selective mu opioid receptor agonist ohmefentanyl (OMF) to rats produced dose-dependent antinociception as assessed with the tail flick test. This analgesia could be blocked by intrathecal (i.t.) injection of the 5-HT1A receptor antagonist spiperone or the 5-HT1C/2 receptor antagonist mianserin, but not by the 5-HT2 receptor antagonist 1-NP or the 5-HT3 receptor antagonist ICS 205-930. The results suggest that the descending 5-HT system is involved in mediating spinal mu opioid analgesia via spinal 5-HT1A and 5-HT1C/2 receptors.
Neuroreport 1994 Dec 20
PMID:Spinal serotonin IA and IC/2 receptors mediate supraspinal mu opioid-induced analgesia. 769 28

A series of pyrido[1,2-alpha]indol-6(7-H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The structural requirements for the 5-HT3 receptor antagonist have been defined as an aromatic moiety, a basic nitrogen, and a linking acyl group. The (5-methylimidazol-4-yl)methyl group as a basic nitrogen moiety was an important element for high potency. The highest potency was observed for compounds which have 7- and 10-methyl substituents on the pyrido[1,2-alpha]indol-6(7H)-one ring. From this series, (+)-11b (FK 1052) was selected for further evaluation. FK 1052 was a potent 5-HT3 receptor antagonist in the Bezold-Jarisch reflex test in rats (ED50 0.9 microgram/kg, i.v.) and a very effective antiemetic agent against cisplatin-induced emesis in dogs (ED50 1.2 x 2 micrograms/kg, i.v. and 2.7 x 2 micrograms/kg, p.o.).
Chem Pharm Bull (Tokyo) 1994 Dec
PMID:New 5-HT3 (serotonin-3) receptor antagonists. I. Synthesis and structure-activity relationships of pyrido[1,2-a]indoles. 769 71

A series of pyrimido[1,6-alpha]indol-1(2H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The compounds in this series were regarded as bioisosters of the pyrido[1,2-alpha]indol-6(7H)-ones previously reported. High potency was found for compounds having 5-methyl substituents on both the pyrimido[1,6-alpha]indole ring and the imidazole ring. Optimized members of this series, 8b and (+)-26a, were potent 5-HT3 receptor antagonists as determined by measuring inhibition of the Bezold-Jarisch reflex in anesthetized rats (ED50 0.6 and 0.8 microgram/kg i.v., respectively), being equipotent to or more potent than FK 1052 (1) in the previous paper and 20- to 30-fold more potent than ondansetron (2).
Chem Pharm Bull (Tokyo) 1994 Dec
PMID:New 5-HT3 (serotonin-3) receptor antagonists, II. Synthesis and structure-activity relationships of pyrimido[1,6-a]indoles. 769 72

The present study investigated the effects of various classes of antidepressant drugs (10 mg/kg per day, s.c. during 21 days) on the electrically evoked release of [3H]noradrenaline and on its modulation by the 5-HT3 receptor agonist 2-methyl-5-hydroxy-tryptamine (2-methyl-5-HT) using preloaded rat hippocampal slices. Treatments with either fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, or moclobemide, a reversible type A monoamine oxidase inhibitor, increased the evoked release of [3H]noradrenaline. These two antidepressant treatments did not change, however, the magnitude of the enhancing effect of 2-methyl-5-HT on the electrically evoked release of [3H]noradrenaline. Desipramine produced a much larger increase of the electrically evoked release of [3H]noradrenaline than fluoxetine or moclobemide, and desensitized the 5-HT3 receptors that modulate this release. Trimipramine, which like desipramine has a tricyclic structure but does not block the reuptake of noradrenaline or that of 5-HT, did not increase the evoked release of [3H]noradrenaline and did not desensitize the 5-HT3 receptors that enhance the release of [3H]noradrenaline. Maprotiline, a selective noradrenaline reuptake inhibitor, did not produce the same changes as desipramine, but maprotiline inhibited noradrenaline reuptake to a lesser extent (50%) than desipramine (80%). These results suggest that the high potency noradrenaline reuptake blocker desipramine desensitizes 5-HT3 receptors modulating [3H]noradrenaline release, but that this effect is not common to all antidepressant drugs.
Eur J Pharmacol 1994 Dec 12
PMID:Effect of long-term administration of antidepressant drugs on the 5-HT3 receptors that enhance the electrically evoked release of [3H]noradrenaline in the rat hippocampus. 769 95

The antagonistic activities of compound N-3389 (endo-3,9-dimethyl-3,9- diazabicyclo[3,3,1]non-7-yl 1H-indazole-3-carboxamide dihydrochloride) at 5-HT3 and 5-HT4 receptors were examined using in vitro and in vivo assays. N-3389 showed potent 5-HT3 receptor antagonistic activities in a radioligand binding assay (pKi = 8.77), against 2-methyl-5-HT (2-Me-5-HT)-induced bradycardia in rats (ED50 = 0.73 micrograms/kg i.v., 38 micrograms/kg p.o.) and against 2-Me-5-HT-induced contraction in longitudinal muscle myenteric plexus preparations of guinea-pig ileum (IC50 = 3.2 x 10(-8) M). As a preliminary to investigating the effect of N-3389 on 5-HT4 receptors, we examined the contraction induced by 5-HT in guinea-pig ileum preparations. We confirmed that 5-HT (10(-8)-10(-5) M) induced biphasic contractions in the preparations. Furthermore, 5-HT3 receptor antagonism inhibited the late phase of the contraction induced by high concentrations of 5-HT (3 x 10(-6)-10(-5) M), whereas 5-HT4 receptor antagonism inhibited the early phase of the contraction induced by low concentrations of 5-HT (10(-8)-10(-6) M). N-3389 (10(-7)-10(-5) M) inhibited both phases of contraction induced by 5-HT. In addition, N-3389 (3 x 10(-7)-3 x 10(-6) M) was found to inhibit the increase of electrically stimulated twitch responses induced by 5-HT (10(-8) M) longitudinal muscle myenteric plexus preparation of the guinea-pig ileum. These results suggest that N-3389 acts as a 5-HT3 and 5-HT4 receptor antagonist.
Eur J Pharmacol 1994 Dec 12
PMID:Antagonistic activities of N-3389, a newly synthesized diazabicyclo derivative, at 5-HT3 and 5-HT4 receptors. 769 98

1. The actions of 5-hydroxytryptamine (5-HT) on rat dentate gyrus neurones were measured with conventional intracellular recording techniques in brain slices maintained in vitro at 32 degrees C. 2. Bath application of 5-HT (0.3-100 microM) hyperpolarized the membrane potential and reduced the input resistance; these effects persisted in tetrodotoxin (1 microM) and were abolished by MDL 73,005EF, a 5-HT1A receptor antagonist. 3. Local application of 5-HT via a pressure pipette also elicited a hyperpolarization and a reduction in resistance, and evoked a transient 'burst' of spontaneous inhibitory postsynaptic potentials (IPSPs) which were blocked by tetrodotoxin or bicuculline. 4. The 'burst' of IPSPs was subject to desensitization. It was completely abolished in the presence of the 5-HT3 receptor antagonist dolasetron. 5. In some cells, a longer lasting increase in spontaneous IPSP frequency was observed during application of 5-HT; this effect was blocked by the 5-HT2 receptor antagonist MDL 100,907. 6. 5-HT (30 microM) shortened the decay time constants of the glutamatergic and GABAergic evoked EPSPs and IPSPs without changing their amplitudes. 7. It is concluded that 5-HT hyperpolarizes granule cells via postsynaptic 5-HT1A receptors and increases spontaneous GABA release from inhibitory interneurones via the activation of 5-HT3 receptors and/or 5-HT2 receptors.
J Physiol 1994 Dec 15
PMID:Transient and long-lasting actions of 5-HT on rat dentate gyrus neurones in vitro. 770 31

1. The aim of the present study was to determine the role of 5-HT3 receptors of the gastroprotective effect of salmon calcitonin (sCT) and sCT-induced changes in gastric, hepatic, brain and brainstem glutathione (GSH) and lipid-peroxidation (LP) levels in rats subjected to cold-immobilization stress. 2. Stress exposure resulted in ulcer formation and a decrease in GSH levels of the liver, brain and brainstem and an increase in gastric and hepatic LP (P < 0.05). 3. sCT prevented stress-induced gastric ulcer development (P < 0.01) and reversed the decrease in hepatic and brain GSH levels (P < 0.05). 4. In the present study, a 5-HT3 receptor antagonist, ICS 205,930 was used. Interestingly, the effect of the blocker on GSH and LP levels of the tissues studied was similar to those of sCT. 5. ICS 205,930 dose dependently reversed the anti-ulcer effect of sCT although it did not antagonize the effect of sCT on GSH and LP levels, but it seemed to show an additive interaction for brain and brainstem GSH and gastric LP levels with sCT.
Gen Pharmacol 1994 Dec
PMID:The role of 5-HT3 receptors in the anti-ulcer effect of calcitonin. 772 Oct 34

The effect of acute exposure to alcohols on ion current mediated by recombinant 5-HT3RA receptors transiently expressed in human embryonic kidney 293 cells was investigated. Cells transfected with 5-HT3RA cDNA expressed receptors with pharmacological and functional properties similar to those of native 5-HT3 receptors. Potentiation of receptor-mediated cation current was observed in the presence of ethanol (10-100 mM), butanol (0.1-20 mM), isopentanol (0.01-25 mM) and trichloroethanol (0.5-25 mM). Potentiation increased in a concentration-dependent manner until saturation was achieved for all alcohols tested. The maximal efficacies of potentiation differed among the alcohols with isopentanol > butanol = trichloroethanol > ethanol. Potentiation by butanol and isopentanol appeared to show acute tolerance such that the percent increase in current amplitude was largest upon the first of a series of alcohol applications and decreased during subsequent applications. The effect of ethanol was variable with potentiation occurring in 74% of cells examined, but not in the remaining cells. These observations indicate that the potentiating action of alcohols is similar in recombinant receptors to that previously observed in neuroblastoma cells and neurons expressing native receptors. These findings indicate that this recombinant system is suitable for studying the molecular basis of alcohol actions on the 5-HT3 receptor.
Neuropharmacology 1994 Dec
PMID:Alcohols potentiate ion current mediated by recombinant 5-HT3RA receptors expressed in a mammalian cell line. 776 Sep 80


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