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At least 235 records · Page 13Linked to original sources
PubMed2000

Maitotoxin stimulates Cd influx in Madin-Darby kidney cells by activating Ca-permeable cation channels.

This study examined the role of calcium channels for the uptake of cadmium (Cd) into Madin-Darby canine kidney (MDCK) cells. Maitotoxin, an activator of different types of calcium channels, increased accumulation of 109Cd and 45Ca in MDCK cells. We found that maitotoxin increased accumulation by stimulating 109Cd influx because it did not affect efflux. An inhibitor of store-operated Ca channels, SKF96365, partially blocked 45Ca influx but did not affect 109Cd influx. Ni and Mn, and loperamide and proadifen (SKF 525a), inhibited 45Ca and 109Cd influx in cells stimulated with maitotoxin, but La and nifedipine did not. Overnight treatment with phorbol 12, 13-ibutyrate (PDBu) to activate protein kinase C resulted in a decrease in the concentration of maitotoxin needed to stimulate 45Ca and 109Cd influx. The effect of PDBu was blocked by treating cells with the protein kinase C inhibitor GF109203X. Additionally, the effect of PDBu was lost in cells treated with an inhibitor of RNA synthesis actinomycin D. These results suggest that a Ca permeable cation channel different from voltage-dependent and store-operated Ca channels mediates the uptake of Cd in MDCK cells. The expression of this channel is regulated by protein kinase C.

Animals↗
PubMed2005

A toxic extract of the marine phytoflagellate Prymnesium parvum induces calcium-dependent release of glutamate from rat brain synaptosomes.

Blooms of the marine phytoflagellate Prymnesium parvum produced mass mortality of fish in Norway and many other parts of the world. The effects of a purified algae extract of P. parvum on transmitter release from rat brain synaptosomes were studied to characterize its toxic action. Synaptosomes are detached nerve terminals and represent a simple system that has retained the machinery for uptake, synthesis, storage, and release of neurotransmitters. A crude methanol extract of P. parvum was purified by reverse-phase column for fast protein liquid chromatography (FPLC). The purified extract stimulated Ca2+-dependent spontaneous release of glutamate in a concentration-dependent manner. The release was increased by addition of extracellular Ca2+. The release of glutamate was suppressed by the Ca2+-channel blockers flunarizine (10 microM), diltiazem (10 microM), and verapamil (10 microM). The stimulation of release of glutamate from rat brain synaptosomes induced by the toxin may be due to an ionophorelike property of the algae extract such as previously reported for the potent algal toxin maitotoxin. At high concentrations the toxin primarily acts as a powerful lytic agent.

Animals↗
PubMed1988

Some chemical properties of maitotoxin, a putative calcium channel agonist isolated from a marine dinoflagellate.

Maitotoxion, a putative Ca2+ channel agonist, was isolated from cultures of the marine dinoflagellate Gambierdiscus toxicus as a colorless amorphous solid. The toxin reacted positively to Dragendorff's reagent but not to ninhydrin reagent. The mouse lethality of maitotoxin determined by intraperitoneal injection was 0.13 micrograms/kg. Chemical features of the toxin were elucidated mainly by various spectroscopic measurements. The molecular weight of maitotoxin as a disodium salt was estimated to be 3,424.5 +/- 0.5 from the negative fast atom bombardment (FAB) mass spectrum. The presence of two sulfate ester groups in the molecule was apparent from the IR and mass spectra, and from analyses of solvolysis products. Despite of its large size, maitotoxin seems to have no known repeating units, such as amino acids and sugars, no carbonyl groups, no side chains other than methyls or an exomethylenes, and no carbocycles.

Animals↗
PubMed1990

Increased intracellular calcium stimulates 3H-inositol polyphosphate accumulation in rat cerebral cortical slices.

Agents that increase the intracellular Ca2+ concentration have been examined for their ability to stimulate 3H-inositol polyphosphate accumulation in rat cerebral cortex slices. Elevated extracellular K+ levels, the alkaloid sodium channel activator veratrine, the calcium ionophore ionomycin, and the marine toxin maitotoxin were all able to stimulate phosphoinositide metabolism. Certain features appear common to the agents studied. Thus, although [3H]inositol monophosphate, [3H]inositol bisphosphate ([3H]InsP2), and [3H]inositol trisphosphate were all stimulated, a proportionally greater effect was observed on [3H]InsP2 in comparison to stimulation by the muscarinic receptor agonist carbachol. However, only an elevated K+ level stimulated [3H]inositol tetrakisphosphate ([3H]InsP4) accumulation alone or produced marked synergy with carbachol on the formation of this polyphosphate. The results suggest that agents that elevate the cytoplasmic Ca2+ concentration in cerebral cells can increase the hydrolysis of membrane polyphosphoinositides. The pattern of the response differs from that produced by muscarinic receptor agonists and indicate that Ca2(+)-dependent hydrolysis may involve different pools of lipids, phosphoinositidase C enzymes, or both. However, clear differences in the ability of these agents to stimulate InsP4, alone or in the presence of muscarinic agonist, suggest that factors other than a simple elevated intracellular Ca2+ concentration are implicated.

Animals↗
PubMed1985

Brevetoxin-B of Gymnodinium breve toxin-induced contractions of smooth muscles due to the transmitter release from nerves.

Brevetoxin-B (BTX-B), a Gymnodinium breve toxin, isolated from the dinoflagellate, produced contraction of guinea pig ileum and rabbit aorta. Atropine (10(-6) M) and phentolamine (10(-6) M) abolished the BTX-B (10(-7) or 10(-6)-induced contraction of the ileum or aorta, respectively. Tetrodotoxin and saxitoxin (both 5 x 10(-7) M) also abolished the responses to BTX-B in the both tissues. Results suggest that BTX-B produces smooth muscle contractions through the tetrodotoxin- and saxitoxin-sensitive release of transmitters from autonomic nerves.

Animals↗
PubMed2002

Blockade of maitotoxin-induced oncotic cell death reveals zeiosis.

BACKGROUND: Maitotoxin (MTX) initiates cell death by sequentially activating 1) Ca2+ influx via non-selective cation channels, 2) uptake of vital dyes via formation of large pores, and 3) release of lactate dehydrogenase, an indication of cell lysis. MTX also causes formation of membrane blebs, which dramatically dilate during the cytolysis phase. To determine the role of phospholipase C (PLC) in the cell death cascade, U73122, a specific inhibitor of PLC, and U73343, an inactive analog, were examined on MTX-induced responses in bovine aortic endothelial cells. RESULTS: Addition of either U73122 or U73343, prior to MTX, produced a concentration-dependent inhibition of the cell death cascade (IC50 asymptotically equal to 1.9 and 0.66 microM, respectively) suggesting that the effect of these agents was independent of PLC. Addition of U73343 shortly after MTX, prevented or attenuated the effects of the toxin, but addition at later times had little or no effect. Time-lapse videomicroscopy showed that U73343 dramatically altered the blebbing profile of MTX-treated cells. Specifically, U73343 blocked bleb dilation and converted the initial blebbing event into "zeiosis", a type of membrane blebbing commonly associated with apoptosis. Cells challenged with MTX and rescued by subsequent addition of U73343, showed enhanced caspase-3 activity 48 hr after the initial insult, consistent with activation of the apoptotic program. CONCLUSIONS: Within minutes of MTX addition, endothelial cells die by oncosis. Rescue by addition of U73343 shortly after MTX showed that a small percentage of cells are destined to die by oncosis, but that a larger percentage survive; cells that survive the initial insult exhibit zeiosis and may ultimately die by apoptotic mechanisms.

Animals↗
PubMed1984

Depolarizing action of a red-tide dinoflagellate brevetoxin on axonal membranes.

The neurotoxic actions of T17 , a toxin isolated from the red-tide dinoflagellate Ptychodiscus brevis, on membrane excitability were investigated by the intracellular microelectrode technique on the crayfish giant axons and by the voltage clamp experiments on the squid giant axons. External application of T17 toxin caused a concentration-dependent depolarization, transient repetitive discharges, followed by depression of the action potential leading to a complete block of excitability. The reversibility of the depolarizing action upon washing decreased as the time of toxin treatment was increased. The T17 -induced depolarization was effectively reversed by 0.3 microM tetrodotoxin or 1 mM Na external solution. Pretreatment with tetrodotoxin completely antagonized the T17 depolarizing action. However, upon washing the axon with the normal external solution, depolarization occurred. Pretreatment with either procaine or dibucaine at high doses also offered protection against the depolarization. The toxin action was greatly potentiated by the sea anemone toxin, anthopleurin-A. The voltage clamp experiments showed that T17 toxin affected sodium current only. The activation voltage for sodium current was shifted in the hyperpolarizing direction by more than 35 mV. T17 toxin also greatly depressed the fast inactivation of sodium current. However, there was no significant change in the kinetics of the sodium tail current. These results indicate that T17 toxin depolarizes the membrane by selectively opening sodium channels at fairly negative potentials and by inhibiting the fast sodium inactivation. We also infer that the binding site for T17 toxin is different from those for tetrodotoxin and sea anemone toxin.

Anesthetics, Local↗
PubMedDate not supplied

Detection of marine toxins using reconstituted sodium channels.

Specific binding of the marine toxins saxitoxin, tetrodotoxin, and brevetoxin to the rat brain sodium channel is demonstrated using purified sodium channels reconstituted into phospholipid vesicles. Restoration of sodium channel function and binding activity by incorporation into phospholipid vesicles provides the only rigorous proof that the purified protein contains the neurotoxin receptor sites. In addition, reconstitution provides a valuable experimental preparation for biochemical analysis of neurotoxin binding sites and may facilitate the development of a specific toxin detection system.

Animals↗
PubMed1997

Analysis of brevetoxins by micellar electrokinetic capillary chromatography and laser-induced fluorescence detection.

Micellar electrokinetic capillary chromatography (MEKC) with laser-induced fluorescence (LIF) detection was used to measure four red tide brevetoxins at sub-attomole levels. The separation of four brevetoxins by MEKC was achieved with a sodium borate/sodium dodecyl sulfate buffer at pH 9.3 Brevetoxins with a terminal alcohol group were derivatized with an acyl azide coumarin to form stable, highly fluorescent products. Brevetoxins with a terminal aldehyde group were reduced to the alcohol with sodium borohydride prior to derivatization with the coumarin. Three derivatized brevetoxins (PbTx-3, PbTx- 5, and PbTx-9) were separated by MEKC and detected using He/Cd laser excitation at 354 nm and fluorescence emission at 410 nm. A fourth brevetoxin (PbTx-2) was converted to PbTx-3 prior to derivatization and was then determined by subtraction. Instrumental detection limits for all four toxins were approximately 0.10 fg or about 10(6)-fold more sensitive than existing liquid chromatographic methods. Brevetoxins were isolated from cell cultures and fish tissue using an alumina column/gel-permeation chromatography procedure. Method detection limits for the brevetoxins in fish tissue were approximately 4 pg/g. These method detection limits are at least 100-fold better than previous chromatographic and/or electrophoretic methods. The MEKC-LIF method reported here allows measurement of brevetoxins at the trace levels considered critical for understanding toxin metabolism and mode of action.

Animals↗
PubMed2006

Improved protonation, collision-induced decomposition efficiency and structural assessment for 'red tide' brevetoxins employing nanoelectrospray mass spectrometry.

Brevetoxins are a group of natural neurotoxins found in blooms of red tide algae. Previous electrospray mass spectrometry (ES-MS) studies show that all brevetoxins have high affinities for sodium ions, and they form abundant sodium adduct ions, [M + Na]+, in ES-MS, even when trace contamination is the only source of sodium ions. Attempts to obtain informative product ions from the collision-induced decomposition (CID) of [M + Na]+ brevetoxin precursor ions resulted only in uninformative sodium ion signals, even under elevated collision energies. In this study, a nano-ES-MS approach was developed wherein ammonium fluoride was used to form cationic [M + NH4]+ adducts of brevetoxin-2 and brevetoxin-3; a significant increase in the abundance of protonated brevetoxin molecules [M + H]+ also resulted, whereas the abundance of sodium adducts of brevetoxins [M + Na]+ was observed to decrease. Under CID, both [M + NH4]+ and [M + H]+ gave similar, abundant product ions and thus underwent the same types of fragmentation. This indicated that ammonium ions initially attached to brevetoxins forming [M + NH4]+ easily lose neutral ammonia in a first step in the gas phase, leaving protonated brevetoxin [M + H]+ to readily undergo further fragmentation under CID.

Animals↗
PubMed1987

Maitotoxin stimulates phosphoinositide breakdown in neuroblastoma hybrid NCB-20 cells.

1. Maitotoxin (MTX) was an extraordinarily potent stimulant of phosphoinositide breakdown in the neuroblastoma hybrid NCB-20 cells. 2. Maximal responses were obtained at 0.25-0.5 ng MTX/ml, and resulted in increased formation of [3H]inositol mono-, bis-, and trisphosphates. Increased formation of [3H]inositol bis- and trisphosphate was observed as early as 15 sec after the addition of MTX. 3. MTX-induced phosphoinositide breakdown in NCB-20 cells was not antagonized by organic (nifedipine, methoxyverapamil) or inorganic (Mn2+, Co2+, Cd2+) calcium channel blockers. However, the response on phosphoinositide breakdown was completely eliminated in the absence of extracellular calcium. 4. The results suggest that MTX either directly stimulates phosphoinositide breakdown in a calcium-dependent manner or acts indirectly through calcium channels insensitive to organic/inorganic calcium channel blockers.

Animals↗
PubMed2005

Cochlear function in mice following inhalation of brevetoxin-3.

Brevetoxin-3 was shown previously to adversely affect central auditory function in goldfish. The present study evaluated the effects of exposure to this agent on cochlear function in mice using the 2f(1)-f(2) distortion-product otoacoustic emission (DPOAE). Towards this end, inbred CBA/CaJ mice were exposed to a relatively high concentration of brevetoxin-3 (approximately=400 microg/m(3)) by nose-only inhalation for a 2-h period. Further, a subset of these mice received a second exposure a day later that lasted for an additional 4 h. Mice exposed only once for 2 h did not exhibit any notable cochlear effects. Similarly, mice exposed two times, for a cumulative dose of 6 h, exhibited essentially no change in DPOAE levels.

Acoustic Stimulation↗
PubMed1986

Maitotoxin and Bay-K-8644: two putative calcium channel activators with different effects on endogenous dopamine release from tuberoinfundibular neurons.

In the present study we report on the effects of two putative calcium channel activators, maitotoxin and the dihydropyridine BAY-K-8644, on endogenous dopamine release from tuberoinfundibular dopaminergic neurons. Maitotoxin stimulated basal dopamine release and this effect was calcium-dependent. By contrast BAY-K-8644 failed to produce any modification of basal or high potassium-induced dopamine release. These results suggest that maitotoxin, unlike BAY-K-8644, represents a suitable tool to investigate the functional role of calcium channels in central dopaminergic neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Ciguatoxin and brevetoxins share a common receptor site on the neuronal voltage-dependent Na+ channel.

Binding studies indicate that ciguatoxin and brevetoxin allosterically enhance in a very similar way the binding of [3H]batrachotoxinin A 20-alpha-benzoate to the neuronal Na+ channel protein. Moreover ciguatoxin competitively inhibits the binding of [3H]brevetoxin-3 to rat brain membranes. The affinity of ciguatoxin for the Na+ channel is at least 20-50-times higher than that of brevetoxin. These results indicate that ciguatoxin and brevetoxins act at the same binding site on the sodium channel.

Animals↗