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

[131I]metaiodobenzylguanidine ([131I]MIBG) is selectively taken up and stored by tumours derived from the neural crest, and is used for diagnosis and treatment of neuroblastoma (NB). The antitumoral effect of [131I]MIBG is closely related to the intracellular level of the radiopharmaceutical compound, which is dependent on uptake and storage/release mechanisms. While MIBG uptake is well characterised, storage and release mechanisms are still controversial. In order to better characterise [125I]MIBG release mechanisms, we studied the basal and stimulated efflux of [125I]MIBG in the human NB cell line, SH-SY5Y, preloaded with 0.1 microM [125I]MIBG for 1 h. We found that [125I]MIBG basal efflux is highly temperature-dependent, that [125I]MIBG release, induced by cell depolarisation with high potassium, is mainly calcium-independent, and induced by exchange with cold MIBG or noradrenaline, inversion of the sodium gradient across the cell membrane by veratridine by substitution of sodium chloride with equimolar concentration of lithium chloride. The exposure of NB cells to imipramine, an Uptake-1 inhibitor, also produces a net stimulatory effect on [125I]MIBG release. However, when used in association with other releasing stimuli, such as higher levels of intracellular sodium or external agonists, imipramine abolishes the consequent increase of [125I]MIBG release. Our findings suggest that stimulated [125I]MIBG release is mediated by a carrier, most probably the uptake carrier working in a reverse mode, while a minimal fraction of [125I]MIBG is released by an exocytotic mechanism.
 ...
PMID:Release mechanisms of [125I]meta-iodobenzylguanidine in neuroblastoma cells: evidence of a carrier-mediated efflux. 757 75

Connexins form a variety of gap junction channels that vary in their developmental and tissue-specific levels of expression, modulation of gating by transjunctional voltage and posttranslational modification, and unitary channel conductance (gamma j). Despite a 10-fold variation in gamma j, whether connexin-specific channels possess distinct ionic and molecular permeabilities is presently unknown. A major assumption of the conventional model for a gap junction channel pore is that gamma j is determined primarily by pore diameter. Hence, molecular size permeability limits should increase and ionic selectivity should decrease with increasing channel gamma j (and pore diameter). Equimolar ion substitution of 120 mmol/L KCl for potassium glutamate was used to determine the unitary conductance ratios for rat connexin40 and connexin43, chicken connexin43 and connexin45, and human connexin37 channels functionally expressed in communication-deficient mouse neuroblastoma (N2A) cells. Comparison of experimental and predicted conductance ratios based on the aqueous mobilities of all ions according to the Goldman-Hodgkin-Katz current equation was used to determine relative anion-to-cation permeability ratios. Direct correlation of junctional conductance with dye transfer of two fluorescein-derivatives (2 mmol/L 6-carboxyfluorescein or 2',7'-dichlorofluorescein) was also performed. Both approaches revealed a range of selectivities and permeabilities for all five different connexins that was independent of channel conductance. These results are not consistent with the conventional simple aqueous pore model of a gap junction channel and suggest a new model for connexin channel conductance and permselectivity based on electrostatic interactions. Divergent conductance and permeability properties are features of other classes of ion channels (eg, Na+ and K+ channels), implying similar mechanisms for selectivity.
 ...
PMID:Selectivity of connexin-specific gap junctions does not correlate with channel conductance. 758 29

In SH-SY5Y human neuroblastoma cells, addition of acetylcholine or carbachol rapidly induces a transient protrusion of lamellipodia. The protrusions appear after a delay of 30 sec and persist for a period of about 5 min at the margins of cell somata and at the distal parts of cell processes. They are caused by a strikingly increased, cytochalasin B-sensitive assembly of actin at the cell periphery. They often detach from the substrate, retracting and protruding again. In retinoic acid-induced neuronally differentiated cells, this initialized protrusive activity is restricted to growth cones. d-Tubocurarine does not influence, but atropine totally inhibits the cholinergic induction of the actin-driven protrusions, suggesting that a muscarinic receptor-mediated activation of the phosphoinositol signaling pathway is involved. Depolarization by increase of the potassium concentration and ionophore-mediated Ca(2+)-influx are ineffective to trigger the protrusive and ruffling activity. An identical cytochalasin B-sensitive actin-driven response is caused by treating of the cells with the protein kinase C (PKC) activator 12-myristate-13-acetate. In this case, however, lamellar protrusions are formed after a delay of at least 3 min and are maintained for several days. Incubating the cells with the protein kinase C inhibitor bisindolylmaleide or staurosporine inhibits both the muscarinic receptor-mediated and phorbolester-mediated actin-driven response, suggesting that activated PKC plays a crucial role.
 ...
PMID:Muscarinic receptor-mediated induction of actin-driven lamellar protrusions in neuroblastoma cell somata and growth cones. Involvement of protein kinase C. 765 99

Voltage-activated calcium channel currents were recorded from differentiated human neuroblastoma cells. SK-N-SH-SY5Y (SH-SY5Y) line, using patch-clamp techniques. Experimental solutions were designed to suppress sodium and potassium channel currents, and barium ions were used as the charge carrier. Two distinct types of calcium channel currents (N- and L-like) were identified based on their time-dependent inactivation, pharmacology and single-channel conductances. N- and L-like calcium channel currents were evoked by step depolarizing pulses to potentials more positive than -40 mV from a holding potential of -100 mV. The N-like component showed time-dependent inactivation during maintained depolarization with a time constant of tau f approximately 100 ms, whereas the L-like currents showed very slow inactivation with a time constant of tau s approximately 1,000 ms. Steady-state inactivation of currents evoked from a holding potential of -100 mV had two distinct components. One component involved the reduction of the transient current and had a half-maximal current at approximately -66 mV, whereas the other component involved the reduction of the steady-state current in the range of -35 to 0 mV with a half-maximal current at approximately -17 mV. Bay K 8644 (5 microM), had two distinct actions, one was the increase (50%) of the current associated with a depolarizing pulse to +10 mV. The second action was the increase in the peak amplitude of the tail current and the slowing of the deactivation kinetics. Omega-conotoxin at 1 microM irreversibly reduced the N-like current, sparing a component that was still sensitive to 5 microM Bay K 8644. The single-channel currents recorded with the cell-attached configuration of the patch clamp revealed two distinct conductances: a large approximately 28 pS and a small approximately 16 pS, corresponding to the L- and N-like channels, respectively. Bay K 8644 at 5 microM increased the mean open time of L-like single channel currents without changing single-channel conductance.
 ...
PMID:Two types of high voltage-activated calcium channels in SH-SY5Y human neuroblastoma cells. 768 Sep 40

The potassium channel blocker, 4-aminopyridine (4-AP), stimulates neurotransmitter release via plasma membrane depolarization and subsequent activation of voltage-gated calcium channels. The present study assessed the effects of 4-AP on intracellular calcium levels in the human neuroblastoma cell line CHP-100. Blockade of K+ channels with 4-AP significantly increased intracellular calcium concentration ([Ca2+]i). This increase occurred via activation of plasma membrane Ca2+ channels. The 4-AP induced rise in [Ca2+]i was not inhibited by the L-type Ca2+ channel blocker nifedipine but was sensitive to the N-type Ca2+ channel blocker omega-contotoxin GVIA. Tetrodotoxin did not alter the effect of 4-AP. These results suggest that in CHP-100 cells, following inhibition of K+ channels by 4-AP, N-type Ca2+ channels are activated.
 ...
PMID:Inhibition of K+ channel activity by 4-AP stimulates N-type Ca2+ channels in CHP-100 cells. 791 77

Using a cDNA library from bovine adrenal medulla, and, subsequently, a bovine genomic library, we have isolated the gene coding for a non inactivating potassium channel. This gene encodes a 597-amino acid protein which we have called BAK5 as its sequence is very similar to members of Kv1.5 potassium channel family. Neuroblastoma cells (Neuro-2a cell line) were stably transfected with BAK5 DNA. Protein expression was under the control of a heat-shock promoter. Transfected cells showed a current highly selective for potassium, insensitive to tetraethylammonium but reversibly blocked by 4-aminopyridine. Oocytes injected with BAK5 mRNA also expressed a potassium current with the same characteristics.
 ...
PMID:A delayed rectifier potassium channel cloned from bovine adrenal medulla. Functional analysis after expression in Xenopus oocytes and in a neuroblastoma cell line. 795 20

We have examined the effect of fentanyl on [3H]noradrenaline release in a human neuroblastoma cell preparation, SH-SY5Y. Fentanyl produced a significant, concentration-dependent inhibition of [3H]noradrenaline release with IC50 values of 5.5 x 10(-6) mol litre-1 and 15.5 x 10(-6) mol litre-1 for carbachol- and potassium-evoked release, respectively. The small difference in IC50 between the two evoking stimuli may be explained by the weak binding affinity of fentanyl to muscarinic receptors (Ki = 570 nmol litre-1). The minimum concentrations at which a significant effect was observed were 0.3 x 0.10(-6) mol litre-1 and 10.0 x 10(-6) mol litre-1 for carbachol- and potassium-evoked release, respectively; these values are considerably in excess of the serum concentration of fentanyl required to produce analgesia. Naloxone failed to antagonize the fentanyl inhibition and, furthermore, morphine and an enkephalin had no effect on evoked release, implying a non-opioid receptor mediated effect.
 ...
PMID:Fentanyl inhibits the release of [3H]noradrenaline from SH-SY5Y human neuroblastoma cells. 811 May 61

1. Acetylcholine (ACh) produces two membrane current changes when applied to NG108-15 mouse neuroblastoma x rat glioma hybrid cells transformed (by DNA transfection) to express m1 muscarinic receptors: it activates a Ca(2+)-dependent K+ conductance, producing an outward current, and it inhibits a voltage-dependent K+ conductance (the M conductance), thus diminishing the M-type voltage-dependent K+ current (IK(M)) and producing an inward current. The present experiments were undertaken to find out how far inhibition of IK(M) might be secondary to stimulation of phospholipase C, by recording membrane currents and intracellular Ca2+ changes with indo-1 using whole-cell patch-clamp methods. 2. Bath application of 100 microM ACh reversibly inhibited IK(M) by 47.3 +/- 3.2% (n = 23). Following pressure-application of 1 mM ACh, the mean latency to inhibition was 420 ms at 35 degrees C and 1.79 s at 23 degrees C. Latencies to inhibition by Ba2+ ions were 148 ms at 35 degrees C and 92 ms at 23 degrees C. 3. The involvement of a G-protein was tested by adding 0.5 mM GTP-gamma-S or 10 mM potassium fluoride to the pipette solution. These slowly reduced IK(M), with half-times of about 30 and 20 min respectively, and rendered the effect of superimposed ACh irreversible. Effects of ACh were not significantly changed after pretreatment for 24 h with 500 ng ml-1 pertussis toxin or on adding up to 10 mM GDP-beta-S to the pipette solution. 4. The role of phospholipase C and its products was tested using neomycin (to inhibit phospholipase C), inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4), heparin, and phorbol dibutyrate (PDBu) and staurosporin (to activate and inhibit protein kinase C respectively). Both neomycin (1 mM external) and InsP3 (100 microM intrapipette) inhibited the ACh-induced outward current and/or intracellular Ca2+ transient but did not block ACh-induced inhibition of IK(M). Intrapipette heparin (1 mM) blocked activation of IK(Ca) and reduced Ach-induced inhibitions of IK(M), but also reduced inhibition of ICa via endogeneous m4 receptors. PDBu (with or without intrapipette ATP) and staurosporin had no significant effects.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:On the mechanism of M-current inhibition by muscarinic m1 receptors in DNA-transfected rodent neuroblastoma x glioma cells. 827 Nov 96

Differentiated neuroblastoma cells exhibit both the delayed rectifier potassium current (IK) and the M-current (IM). The present study was designed to determine the roles of protein kinase C (PKC) and of the calmodulin-binding protein 80K/MARCKS, a prominent substrate for PKC and possible regulator of these currents. Neuroblastoma x glioma (NG108-15) hybrid cells transfected with m1 muscarinic receptors were grown with 1% fetal bovine serum (FBS) without the prostaglandin E1 (PGE1) and isobutylmethylxanthine (IBMX) usually added in preparation for electrophysiological studies. Under these conditions, the usual pleomorphism was largely abolished, leaving two populations of small cells with stellate and spherically symmetrical geometries. Whole-cell patch clamping indicated that the two cell types had identical electrophysiological properties, displaying: IK, a small current through a "T-like" Ca2+ channel, and no M-current. Stimulation with carbachol shifted the distribution of cells to a more stellate morphology within 24 hr and later (after 48 hr) reduced the PKC substrate 80K/MARCKS by 22 +/- 7%. In contrast to the stimulation of IK observed with cardiac cells, PKC activation produced only a small inhibition of IK, which was independent of carbachol pretreatment. Thus, PKC and 80K/MARCKS can be dissociated from the regulation of IK in neuroblastoma cells.
 ...
PMID:Whole-cell recording of neuroblastoma x glioma cells during downregulation of a major substrate, 80K/MARCKS, of protein kinase C. 832 Jul 19

Nordihydroguaiaretic acid (NDGA; a lipoxygenase inhibitor), LY-270766 (an inhibitor of 5-lipoxygenase), and the diacylglycerol lipase inhibitor RG 80267 completely eliminated potassium-evoked release of [3H]-noradrenaline ([3H]NA) from the human neuroblastoma clone SH-SY5Y with IC50 values of 10, 15, and 30 microM, respectively. In contrast, these inhibitors only partially inhibited carbachol-evoked release and had little effect on the calcium ionophore A23187-evoked release of NA in this cell line. Arachidonic acid partially inhibited potassium- and A23187-evoked release but did not reverse the inhibition of potassium-evoked release observed in the presence of RG 80267. These studies suggest that arachidonic acid (or its lipoxygenase products) are not important intermediates in the regulation of exocytosis in SH-SY5Y. This conclusion is strengthened by our studies in which SH-SY5Y cells were grown in medium supplemented with bovine serum albumin-linoleic acid (50 microM). Under these conditions there was a selective increase in content of membrane polyunsaturated fatty acids of the omega 6 series, including arachidonic acid; however, these changes did not effect potassium-, veratridine-, carbachol-, or calcium ionophore-evoked release of [3H]NA.
 ...
PMID:Effect of inhibitors of eicosanoid metabolism on release of [3H]noradrenaline from the human neuroblastoma, SH-SY5Y. 845 30


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