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)

The plasma aldosterone response following the administration of drugs with antagonist and agonist activity at Serotonin 3 and 4 (5-HT3&4) receptors has been examined in 9 healthy male volunteers receiving the following four treatments i.v. in a randomised, cross-over sequence: ondansetron 8 mg, granisetron 3 mg, metoclopramide 20 mg, and saline 20 ml. Metoclopramide significantly increased the mean plasma aldosterone level to 196% of basal level at 5 min. It rose to 234% at 15 min and remained at more than 185% of basal level for the duration of the experiment. The response to ondansetron and granisetron did not differ significantly from placebo. If dopamine antagonism is discounted, the results suggest that metoclopramide-induced aldosterone secretion results from its agonist activity at 5-HT4 receptors, although slow neuronal depolarization via an unidentified receptor remains a possibility. Antagonism at the 5-HT3 receptor plays no role, as the selective antagonist, granisetron, did not elicit a significant response. It seems unlikely that the 5-HT4 receptor is the second, low affinity binding site of ondansetron, unless it had no agonist activity at this receptor.
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PMID:Effect of metoclopramide, ondansetron and granisetron on aldosterone secretion in man. 839 Mar 68

Effects of some naturally occurring steroids and synthetic analogues on the cation flux through the cation channel of the 5-HT3 receptor and the voltage-gated and tetrodotoxin-sensitive sodium channel were studied in N1E-115 mouse neuroblastoma cells by measuring the 2-min influx of the organic cation [14C]-guanidinium. The cation fluxes in intact cells were either induced by 2 min exposure of the cells to 5-hydroxytryptamine (5-HT, 100microM) or to veratridine (1 mM). Influx of [14C]-guanidinium through both channels was concentration-dependently inhibited by all compounds studied. The rank order of potency for inhibition of the 5-HT3 receptor-induced cation flux was clomiphene approximately/= cyproterone acetate > estradiol > progesterone approximately/= allotetrahydrodeoxycorticosterone > alfaxalone approximately/= testosterone > aldosterone > dexamethasone. With the exception of dexamethasone and testosterone, which were more potent at the voltage-dependent sodium channel, and progesterone and testosterone, which were about nearly equipotent in inhibiting both cation channels, the steroids were twofold (alfaxalone, allotetrahydrodeoxycorticosterone) to 107-fold (cyproterone acetate) more potent at the 5-HT3 receptor channel than at the voltage-gated sodium channel. The potencies of the steroids (and the synthetic analogues) for inhibition of the 5-HT3 receptor-induced [14C]-guanidinium influx were correlated with their lipophilicity (log P values). A similar correlation between log P values and pIC50 values for the steroid-induced inhibition of the veratridine-evoked cation influx through the voltage-gated sodium channel was only found when cyproterone acetate (a compound with extremely low inhibitory potency at this channel) was not included in the regression analysis. The results indicate that both the 5-HT3 receptor channel and the voltage-gated sodium channel are targets for steroids. The relationship between most of the compounds in inhibiting both cation channels and lipophilicity is compatible with a common mechanistic principle in steroid-induced inhibition of the two channels, i.e. a nonspecific hydrophobic interaction with certain membrane lipids in the neighbourhood of the two channels.
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PMID:Inhibition by steroids of [14C]-guanidinium flux through the voltage-gated sodium channel and the cation channel of the 5-HT3 receptor of N1E-115 neuroblastoma cells. 1054 23