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

The role of 5-HT3 receptors in the control of intestinal propulsive activity was investigated in mice by a simple method in which the time taken for excretion of the head of an orally administered non-absorbable marker (whole gut transit time) was measured. Selective 5-HT3 receptor antagonists ramosetron (YM060) at 0.01-0.3 mg/kg s. c. and ondansetron at 0.1-1 mg/kg s.c. dose-dependently prolonged the whole gut transit time. Prokinetic benzamides, such as renzapride (0.3-10 mg/kg s.c.), zacopride (0.01-0.3 mg/kg s.c.) and cisapride (0.1-3 mg/kg s.c.), which have been reported to possess 5-HT3 receptor blocking properties, also dose-dependently prolonged it. These results indicate that activation of 5-HT3 receptors seems to be one factor that underlies the physiological control of intestinal propulsive activity in mice. In contrast to their beneficial therapeutic effects on gastroduodenal dysmotility, prokinetic benzamides, at least those which have 5-HT3 receptor antagonistic activity, may be unsuitable in the treatment of impaired lower intestinal propulsive activity.
Eur J Pharmacol 1996 Sep 05
PMID:Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice. 888 38

Prolactin responses to d-fenfluramine (d-FEN) challenge (0.5 mg/kg PO) were examined after pre-treatment with and without the 5-HT3 receptor antagonist ondansetron (16 mg PO) in 11 physically healthy male volunteers. Compared to pretreatment with placebo, pre-treatment with ondansetron did not significantly attenuate the PRL response to d-FEN challenge. These data are consistent with other data suggesting little role for 5-HT3 receptors in the PRL response to 5-HT agonist challenge in human subjects.
Psychopharmacology (Berl) 1996 Sep
PMID:5-HT3 receptor antagonism by ondansetron does not attenuate prolactin response to d-fenfluramine challenge in healthy human subjects. 888 75

The aim of the study was to further characterize the pharmacological properties of 5-hydroxytryptamine (5-HT)3-like receptors in the rat medial prefrontal cortex (mPFC) using combinations of biochemical and electrophysiological approaches. Phenylbiguanide (PBG) and three chlorinated derivatives, ortho-chloro-PBG (oCPBG), meta-chloro-PBG (mCPBG) and para-chloro-PBG (pCPBG), dose-dependently stimulated phosphoionositide (PI) turnover in fronto-cingulate cortical slices. All three chloro-isomers of PBG were equipotent in stimulating PI turnover. SR 57227A ((4-amino)-(6-chloro-2-pyridyl) L-piperidine hydrochloride, a novel compound with high affinity and selectivity for peripheral and central 5-HT3 receptors) dose-dependently stimulated PI turnover in fronto-cingulate cortical slices. The rank order of potency of all the 5-HT3 receptor agonists tested in the PI assay as compared to 5-HT was: 5-HT > 2-Me-5-HT > SR57227A > PBG = mCPBG = oCPBG = mCPBG. 5-HT and 5-HT receptor agonists depressed the firing rate of both spontaneously active and glutamate-activated quiescent mPFC cells in a current (dose)-dependent fashion. The rank order of effectiveness of these compounds was: 5-HT > SR57227A = 2-Me-5-HT = mCPBG = oCPBG = pCPBG = PBG. Unlike its action on the 5-HT3 receptors in the periphery or cultured cell lines, D-tubocurarine chloride appears to be non-specific in blocking the depressant action of 2-Me-5-HT, gamma-aminobutyric acid and dopamine. Our results combined support the view that the pharmacological properties of 5-HT3-like receptors in the mPFC are not identical to those located in peripheral tissues and in cultured cell lines.
Brain Res 1996 Sep 09
PMID:5-HT3-like receptors in the rat medial prefrontal cortex: further pharmacological characterization. 889 Dec 44

The effects of itasetron (endo-N-8-methyl-8-azabicyclo-[3.2.1.]-octo-3-yl) -2,3-dihydro-2-oxo-1 H-benzimidazole-1-carboxamide hydrochloride), a 5-HT3 receptor antagonist, on discrete memory abilities of the aged rat were assessed by using the multiple choice avoidance behavioral task. Chronic treatment with itasetron (i.p., 10 micrograms/kg, b.i.d., for three consecutive weeks), but not with vehicle, significantly improved retention abilities of the aged rats in this memory test. These results further support the important role of this 5-HT3 receptor antagonist in counteracting age-related memory degeneration in rodents.
Eur J Pharmacol 1996 Sep 12
PMID:Itasetron (DAU 6215) prevents age-related memory deficits in the rat in a multiple choice avoidance task. 889 90

The 5-HT (5-hydroxytryptamine)-induced contractile biphasic concentration-effect curve in rat isolated jejunum was investigated. The pEC50 values for the first and second phases were 8.0 and 6.1, respectively. The responses were insensitive to atropine (0.1 microM), ketanserin (2 microM), (-)-pindolol (5 microM), yohimbine (0.1 microM) and GR 113808 ({1-[2-(methyl-sulphonylamino)ethyl]-4-piperidinyl}methyl 1-methyl-1 H-indole-3-carboxylate, 1 microM) but susceptible to cocaine (10 microM). The low affinity phase was blocked by tetrodotoxin (1 microM), ondansetron (1 microM) and SR48968 (S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide, 0.1 microM). The high affinity phase was antagonised non-surmountably by fluoxetine (1 microM) methysergide (0.1 microM), spiperone (0.1 microM) and methiothepin (0.1 microM). Ritanserin (0.01-0.1 microM) and mesulergine (0.01-0.1 microM) acted as surmountable, competitive antagonists with pA2 values of 8.0 and 8.1, respectively. Clozapine (0.1 microM) was a surmountable antagonist with an apparent pA2 value of 8.0. The rank potency order of the 5-HT receptor agonists was 5-CT (5-carboxyamidotryptamine) > or = 5-HT = 5-methoxytryptamine > or = alpha-methyl-5-HT > > 8-OH-DPAT ((+/-)-2-dipropyl-amino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene) > dipropyl-5-CT > renzapride = sumatriptan. The responses to 5-HT and 5-CT were not potentiated by pargyline (10 and 100 microM). It is suggested that rat jejunum contains a neuronal 5-HT3 receptor facilitating neurokinin release and a contractile smooth muscle 5-HT receptor with a pharmacological operational profile similar to the cloned 5-ht7 receptor.
Eur J Pharmacol 1996 Sep 26
PMID:Characterisation of a postjunctional 5-ht7-like and a prejunctional 5-HT3 receptor mediating contraction of rat isolated jejunum. 889 99

Several human Mendelian diseases, including the long-QT syndrome, malignant hyperthermia, and episodic ataxia/myokymia syndrome, have recently been demonstrated to be due to mutations in ion channel genes. Systematic mapping of ion channel genes may therefore reveal candidates for other heritable disorders. In this study, the GenBank and dbEST databases were used to identify members of several ion channel families (voltage-gated calcium and sodium, cardiac chloride, and all classes of potassium channels). Genes and ESTs without prior map localization were identified based on GDB and OWL database information and 15 genes and ESTs were selected for mapping. Of these 15, only the serotonin receptor 5HT3R had been previously mapped to a chromosome. A somatic cell hybrid panel (SCH) was screened with an STS from each gene and, if necessary the results verified by a second SCH panel. For three ESTs, rodent derived PCR products of the same size as the human STS precluded SCH mapping. For these three, human P1 clones were isolated and the genomic location was determined by metaphase FISH. These genes and ESTs can now be further evaluated as candidate genes for inherited cardiac, neuromuscular and psychiatric disorders mapped to these chromosomes. Furthermore, the ESTs developed in this study can be used to isolate genomic clones, enabling the determination of each transcript's genomic structure and physical map location. This approach may also be applicable to other gene families and may aid in the identification of candidate genes for groups of related heritable disorders.
Somat Cell Mol Genet 1996 Sep
PMID:Chromosomal localization of 15 ion channel genes. 903 51

Serotonin 5-HT3 receptors (5-HT3Rs) are ligand-gated ion channels expressed by many peripheral neurons and are involved in several physiological processes. To learn more about the developmental regulation of 5-HT3R expression, we investigated rat sympathetic and vagal sensory neurons. We found that sympathetic and sensory neurons differ in their regulation of 5-HT3R expression during early postnatal life and as these neurons develop in culture. In SCG neurons 5-HT3R transcript levels are low at postnatal day 1 (P1) and increase 7.5-fold by P21; this increase occurs even after elimination of preganglionic innervation. In comparison, 5-HT3R mRNA levels in P1 nodose neurons are over 14-fold greater than in P1 SCG and change little by P21. We show that 5-HT3R transcript levels in nodose neurons depend on intact target innervation and drop by 60% after axotomy. When P1 SCG neurons develop in culture, we observed a significant increase in 5-HT3R expression: after 7 d in culture, transcript levels increase ninefold versus a threefold increase for neurons developing for 7 d in vivo. In contrast, 5-HT3R mRNA levels in cultured nodose neurons drop by 70% within 24 hr; however, this drop is transient. After 2 d, transcript levels begin to increase, and after 7 d, they are above initial values. We show that this delayed increase in 5-HT3R expression depends on neurotrophins. In both nodose and sympathetic neurons we found that the changes in 5-HT3R gene expression correlate directly with the appearance of 5-HT-evoked current densities.
J Neurosci 1997 Sep 01
PMID:Developing neonatal rat sympathetic and sensory neurons differ in their regulation of 5-HT3 receptor expression. 925 75

Efficacies of the 5-hydroxytryptamine (serotonin) 5-HT3 receptor (5-HT3R) agonists 2-methyl-5-HT, dopamine, and m-chlorophenylbiguanide on 5-HT3R native to N1E-115 cells and on homopentameric 5-HT3R expressed in Xenopus oocytes were determined relative to that of 5-HT. Efficacies of 2-methyl-5-HT and dopamine on 5-HT3R native to differentiated N1E-115 cells are high (54 and 36%) as compared with their efficacies on homopentameric 5-HT3R-A(L) and 5-HT3R-A(S) receptors expressed in oocytes (4-8%). m-Chlorophenylbiguanide does not distinguish between 5-HT3R in N1E-115 cells and in oocytes. The distinct pharmacological profile of 5-HT3R native to differentiated N1E-115 cells is conserved when poly(A)+ mRNA from these cells is expressed in oocytes. The results indicate that, apart from the known 5-HT3R subunits, N1E-115 cells express additional proteins involved in 5-HT3R function.
J Neurochem 1997 Sep
PMID:Native serotonin 5-HT3 receptors expressed in Xenopus oocytes differ from homopentameric 5-HT3 receptors. 928 59

The genes responsible for hereditary paragangliomas (glomus tumors, MIM No. 168000) have been mapped to two distinct loci on the long arm of chromosome 11. Most of the informative families appear to be linked to the distal locus on chromosome 11q23 (PGL1), which has been previously confined to a 2-cM interval by haplotype analysis in an extended Dutch pedigree. To facilitate the identification of the PGL1 disease gene, we constructed an approximately 4-Mb ordered clone contig map of Sequence tagged sites, expressed sequence tags (ESTs), and known genes that spans the PGL1 critical region on chromosome 11q23. Among 29 new positional candidate ESTs, only two (EST100999 and EST241777) mapped within the PGL1 critical region. We further characterized the genomic organization of the promyelocytic leukemia zinc finger (PLZF) gene that maps within the PGL1 critical region and physically excluded the serotonin receptor type 3 (5HT3R) gene. Finally, we identified a common, silent, single-base substitution polymorphism in the 5HT3R gene and characterized the allele sets of two new highly polymorphic microsatellite repeats within the PGL1 critical region.
Genomics 1997 Sep 01
PMID:A high-resolution STS, EST, and gene-based physical map of the hereditary paraganglioma region on chromosome 11q23. 929 38

Intraplantar co-administration of sub-anesthetic doses of bupivacaine (2.5 microg) or lidocaine (7.5 microg) increased the dose- and time-dependent analgesic effects of the 5-HT3 receptor antagonist, 3-a-tropanyl-1-H-indole-3-carboxylic ester (ICS-205 930) (1-100 microg; 50 microl) against inflammatory pain induced by hindpaw inoculation with complete Freund's adjuvant. The effects of bupivacaine were greater than lidocaine at all doses of ICS-205 930 tested. These findings may reflect facilitation of ICS-205 930 effects through negative allosteric modulation by bupivacaine and lidocaine of peripheral 5-HT3 receptors involved in nociceptive processing.
Eur J Pharmacol 1997 Sep 03
PMID:Sub-anesthetic doses of bupivacaine or lidocaine increase peripheral ICS-205 930-induced analgesia against inflammatory pain in rats. 934 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>