Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ionic currents induced by 5-hydroxytryptamine (5-HT) in cultured neuroblastoma N18 cells were studied using whole-cell voltage clamp. The response was blocked by 1-10 nM 5-HT3 receptor-specific antagonists MDL 7222 or ICS 205-930, but not by 1 microM 5-HT1/5-HT2 receptor antagonist spiperone or 5-HT2 receptor-specific antagonist ketanserin. These 5-HT3 receptors seem to be ligand-gated channels because the response (a) did not require internal ATP or GTP, (b) persisted with long internal dialysis of CsF (90 mM), A1F4- (100 microM), or GTP gamma S (100 microM), and (c) with ionophoretic delivery of 5-HT developed with a delay of less than 10 ms and rose to a peak in 34-130 ms. Fluctuation analysis yielded an apparent single-channel conductance of 593 fS. The relative permeabilities of the channel for a variety of ions were determined from reversal potentials. The channel was only weakly selective among small cations, with permeability ratios PX/PNa of 1.22, 1.10, 1.01, 1.00, and 0.99 for Cs+, K+, Li+, Na+, and Rb+, and 1.12, 0.79, and 0.73 for Ca2+, Ba2+, and Mg2+ (when studied in mixtures of 20 mM divalent ions and 120 mM N-methyl-D-glucamine). Apparent permeability ratios for the divalent ions decreased as the concentration of divalent ions was increased. Small monovalent organic cations were highly permeant. Large organic cations such as Tris and glucosamine were measurably permeant with permeability ratios of 0.20 and 0.08, and N-methyl-D-glucamine was almost impermeant. Small anions, NO3-, Cl-, and F-, were slightly permeant with permeability ratios of 0.08, 0.04, and 0.03. The results indicate that the open 5-HT3 receptor channel has an effective minimum circular pore size of 7.6 A and that ionic interactions in the channel may involve negative charges near the pore mouth.
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PMID:Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. 228 32

Twenty-two reported cases of neuroblastoma missed by the mass screening programs were reviewed (six cases in Sapporo City where a quantitative measurement for both vanillylmandelic acid (VMA) and homovanillic acid (HVA) is used and 16 cases in the districts of qualitative judgment only for VMA), and some potential factors for missing a patient were discussed. Most of the 22 patients were diagnosed over 12 mo and had advanced clinical stages at diagnosis (III or IV). Of the 17 cases whose outcome in prognosis was available, nine cases were dead and only three cases were alive without any trace of tumor. Fluctuation in the amounts of urinary VMA and HVA seemed to be one of the causes for missing a patient, especially with a small tumor. The comparison about tumor wt, VMA and HVA amounts, and clinical stage between the 22 true positive cases in Sapporo City and 46 ones in the districts of qualitative methods, and the difference in detection rate between the two groups suggested that the qualitative methods missed more patients with a small tumor. The patients who had abnormally high amounts of HVA with low amounts of VMA accounted for a fairly large part of the missed cases in Sapporo City as well as in the districts of qualitative methods. To the contrary, no patient of this type was found even among the 22 true positive cases in Sapporo City.
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PMID:Cases of neuroblastoma missed by the mass screening programs. 260 40

1 The characteristics of transmembrane currents evoked by 5-hydroxytryptamine (5-HT) in the neuroblastoma x Chinese hamster brain cell line NCB-20 and neuroblastoma clonal cell line N1E-115 have been studied under voltage-clamp conditions by the whole-cell recording and outside-out membrane patch modes of the patch-clamp technique. 2 In 73% of NCB-20 cells examined (n = 221), and all N1E-115 cells studied (n = 80), 5-HT (10 microM) elicited a transient inward current at negative holding potentials, this being associated with an increase in membrane conductance. In both cell lines responses to 5-HT reversed in sign at a potential of approximately -2 mV and demonstrated inward rectification. 3 The reversal potential of 5-HT-induced currents (E5-HT) recorded from either NCB-20 or N1E-115 cells was unaffected by total replacement of internal K+ by Cs+. In N1E-115 cells, reducing internal K+ concentration from 140 to 20 mM produced a positive shift in E5-HT of approximately 28 mV, whereas reducing external Na+ from 143 to 20 mM was associated with a negative shift in E5-HT of about 37 mV. A large reduction in internal Cl- concentration (from 144 to 6 mM) had little effect on E5-HT. 4 5-HT-induced currents of NCB-20 cells were unaffected by methysergide (1 microM) or ketanserin (1 microM), but were reversibly antagonized by GR38032F (0.1-1.0 nM) with an IC50 of 0.25 nM. GR 38032F (0.3 nM) reduced 5-HT-induced currents in N1E-115 cells to approximately 26% of their control value. 5 On outside-out membrane patches excised from both NCB-20 and N1E-115 cells, 5-HT induced small inward currents which could not be clearly resolved into discrete single channel events. Such responses were: (i) reversibly antagonized by GR 38032F (1 nM) (ii) reversed in sign at 0 mV, and (iii) subject to desensitization. 6 Fluctuation analysis of inward currents evoked by 5-HT (1 microM) in N1E-115 cells suggests that 5-HT gates a channel with a conductance of approximately 310fS. Such a relatively small conductance could readily explain why the response of outside-out membrane patches to 5-HT cannot at present be resolved into clear single channel events.
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PMID:The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques. 272 Mar 11

1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor have been studied by use of patch-clamp techniques applied to HEK 293 cells stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of -60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with an inward current. Such currents were unaffected by methysergide (1 microM), or ketanserin (1 microM), but were antagonized in a concentration-dependent and reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 = 440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT) at approximately -2mV and exhibited inward rectification. The influence of extra- and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent, inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic effect with low concentrations enhancing, and high concentrations depressing, the 5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low (1 microM) concentration of 5-HT suggests the current to be mediated by the opening of channels with a conductance of 420 fS. 6. The pharmacological and biophysical properties of the 5-HT3 R-A are similar to those previously described for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception that the function of the recombinant receptor was enhanced by low concentrations of zinc. This observation suggests that the properties of the native receptor are not completely represented by the 5-HT3 R-A subunit alone.
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PMID:An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells. 762 Jul 11