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)

A fast solution exchange system (Dilger and Brett, 1990; Biophysics Journal 57: 723-731) with an exchange rate < 1 msec was used to study 5-HT3 (5-HT; 5-hydroxytryptamine) receptor-mediated currents in superfused outside-out patches of N1E-115 mouse neuroblastoma cells. At negative membrane potentials, 5-HT induced inward currents in a concentration-dependent manner (IC50 = 3.8 microM, Hill coefficient = 1.8). The mean peak current at a near-maximally effective 5-HT concentration of 30 microM was 20.6 pA. The 5-HT3 receptor antagonist ondansetron (0.3 nM) reversibly inhibited the 5-HT (30 microM) signal by approximately 50%. The currents induced during application of 30 microM 5-HT for 2 sec were characterized by inward rectification, a monophasic onset (tau ON = 37.5 msec) and, after reaching a peak, a monophasic decay (desensitization; tau OFF = 391 msec). Onset and decay were slower at lower 5-HT concentrations. The recovery of fully desensitized patches required a washout period of 45 sec. Pentobarbital inhibited 5-HT-induced (30 microM) currents in a concentration-dependent manner. The maximally obtainable inhibition with a given pentobarbital concentration was reached already when it was exclusively coapplied with 5-HT (IC50 = 135 microM. Hill coefficient = -0.7), since additional preexposure for at least 45 sec did not alter the concentration-response curve of pentobarbital. In conclusion, outside-out patches of N1E-115 cells are suitable to study the kinetic properties of 5-HT3 receptor channels. The results obtained in this model with pentobarbital are compatible with the suggestion that the inhibitory action of pentobarbital on 5-HT3 receptors is dependent on the agonist-activated (open) channel.
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PMID:5-HT3 receptors in outside-out patches of N1E-115 neuroblastoma cells: basic properties and effects of pentobarbital. 922 91

Patch-clamp/rapid solution exchange experiments as well as tracer ([14C]-guanidinium) influx measurements were applied to investigate effects of propofol on 5-HT3 receptor channels and compare the results with those obtained with pentobarbital. Currents induced by 30 microM 5-HT were recorded in outside-out patches from N1E-115 cells. Application of propofol 45 s before and during 5-HT application inhibited peak-currents and integrated current responses in a concentration-dependent manner (IC50 values=14.5 and 10.5 microM; Hill coefficients -1.5 and -1.3, respectively). The inhibitory effect of propofol in the current measurements was similar to the propofol-induced inhibition in tracer influx experiments in whole N1E-115 cells (Barann et al., 1993. Naunyn-Schmiedeberg's Archives of Pharmacology 347, 125-132). Pentobarbital-induced inhibition of 5-HT3 receptors in both patch-clamp (Barann et al., 1997. Neuropharmacology 36, 655-664) and tracer influx measurements indicated a lower potency and lower slope (IC50 values=130 and 55 microM; Hill coefficients -0.8 and -0.7, respectively) compared to propofol. Propofol, in contrast to pentobarbital, showed nearly the full potency when applied to the patches exclusively 45 s before 5-HT. Propofol was least effective when administered exclusively during 5-HT. The onset of inhibition of 5-HT-induced peak currents by propofol had a time constant of 220 ms, similar to the kinetics of 5-HT-induced desensitization.
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PMID:Inhibition of 5-HT3 receptors by propofol: equilibrium and kinetic measurements. 1072 17

The patch-clamp technique was used on excised (outside-out) patches to characterize h5-HT3A receptors stably transfected in HEK 293 cells and to compare the effects of the barbiturate anaesthetics methohexital and pentobarbital on this ligand-gated cation channel. At negative membrane potentials 5-HT induced inward currents in a concentration-dependent manner (EC50=8.6 microM, Hill coefficient =1.5). The mean peak current induced by 30 microM 5-HT was -110 pA at -100 mV. The 5-HT3A receptor antagonist ondansetron (0.3 nM) reversibly inhibited the 5-HT (30 microM) signal by 70% and at 3 nM it abolished the response. Methohexital and pentobarbital inhibited 5-HT-induced (30 microM) currents in a concentration-dependent manner. The maximal inhibition with a given methohexital or pentobarbital concentration was reached when the respective drug was applied 45 s prior to and during the 2-s 5-HT pulse (IC50 values=95 microM and 127 microM, Hill coefficient = -1.0 and -1.6, respectively). Although the barbiturates were, thus, equipotent, their effects differed substantially with respect to the dependence on the time schedule of application to the patches: the potency of methohexital was virtually maximal when the drug was applied exclusively 45 s before the agonist pulse, but its inhibitory potency decreased considerably when it was exclusively applied during the 2-s 5-HT pulse (IC50=380 microM). Conversely, pentobarbital was almost maximally potent in inhibiting the 5-HT signal when it was exclusively coapplied with this agonist, but its inhibitory potency was considerably lower (IC50 approximately 500 microM) when applied exclusively 45 s before 5-HT. Another difference between both barbiturates involves the rate of inactivation of 5-HT3 receptor-mediated currents: whereas high concentrations of methohexital (> or = 300 microM) were necessary to induce moderate (< or = twofold) acceleration of this parameter, pentobarbital produced such an effect at all concentrations and the extent of acceleration increased with increasing concentration (1.5- to fivefold). In conclusion, two barbiturates, chemically closely related but of different lipophilicity, clearly differ with respect to the kinetics of their effect on 5-HT3 receptor channels; one possible explanation involves drug access to an amphipathic site of action via both an aqueous and a hydrophobic pathway. Pentobarbital, in contrast to methohexital, inhibits hS-HT3A receptor-mediated currents at anaesthetic concentrations (approximately 90 microM).
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PMID:Recombinant human 5-HT3A receptors in outside-out patches of HEK 293 cells: basic properties and barbiturate effects. 1099 28