Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polyether Toxins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed2001

Synthesis of a 2,9-dioxabicyclo[3.3.1]nonane via double intramolecular hetero-Michael addition: entry to the F-G ring system of the azaspiracids.

[structure: see text]. An effective approach to form a 1,3-disubstituted 2,9-dioxabicyclo[3.3.1]nonane system representing the core of the F and G rings (C28-C34) of the azaspiracid natural products has been developed. The double intramolecular hetero-Michael addition (DIHMA) of a diol upon an ynone generated the bicyclic ketal in a highly diastereoselective fashion.

Alkanes↗
PubMed1992

Cooperative modulation of voltage-dependent sodium channels by brevetoxin and classical neurotoxins in cultured bovine adrenal medullary cells.

The effects of Ptychodiscus brevis toxin (PbTx-3) on 22Na influx, 45Ca influx and catecholamine secretion were examined in cultured bovine adrenal medullary cells and compared with the effects of classical neurotoxins. PbTx-3 alone had no effects, but greatly enhanced veratridine (30 microM)-induced Na influx, Ca influx and secretion, with a EC50 of 30, 25 and 23 nM, respectively. PbTx-3 (1 microM) reduced EC50 values of veratridine approximately 3-fold and increased the maximal responses caused by saturating concentration (300 microM) of veratridine approximately 1.3 fold. alpha- and beta-Scorpion venom shifted the concentration-response curves of veratridine to the left without altering maximal responses. PbTx-3 in combination with either alpha- or beta-scorpion venom showed only additive effects on Na influx, but augmented veratridine (30 microM)-induced Na influx to a greater extent than PbTx-3, alpha- or beta-scorpion venom alone. Na influx due to these toxins was abolished by 1 microM saxitoxin. Our results suggest that Na channels in adrenal medullary cells have neurotoxin receptors for brevetoxin that allosterically stimulate Na influx initiated by veratridine, leading to increased Ca influx and catecholamine secretion. Allosteric interactions do not exist between brevetoxin and alpha-scorpion venom, or between brevetoxin and beta-scorpion venom, but once Na channels are gated by veratridine, these toxins cooperatively augment Na influx.

Adrenal Medulla↗
PubMed1992

Partial structures and binding studies of maitotoxin, the most potent marine toxin.

Partial structures of maitotoxin (MTX) were deduced by extensive two-dimensional NMR measurements, showing that the toxin had carbon-carbon double bonds in both termini of the molecule, and a primary alcohol group at the end. These functionalities were used for preparation of a radioligand of MTX; [3H]H-MTX and [3H]benzoyl-MTX. Both radioligands had high levels of non-specific binding to tissues. The binding of [3H]MTX to rat glioma C6 cells was inhibited by a didesulfo-MTX, suggesting the presence of the specific site for MTX-binding on the external surface of the cell membrane.

Animals↗
PubMed1992

Molecular properties of the sodium channel: a receptor for multiple neurotoxins.

Sodium channels are the receptors for more than 10 distinct classes of biological toxins which act at five or more receptor sites. Brevetoxins and ciguatoxins act at neurotoxin receptor site 5. This receptor site is located on the alpha subunit of the sodium channel, and peptide segments in domain IV of that subunit are important in brevetoxin binding.

Animals↗
PubMed1982

Maitotoxin, a Ca2+ channel activator candidate.

Effects of maitotoxin, the most potent marine toxin, were studied using a rat pheochromocytoma cell line, PC12h. A low concentration (10(-8) g/ml) of maitotoxin induced a profound increase in CA2+ influx into PC12h cells and the Ca2+-dependent release of [3H]norepinephrine from them. The effects of maitotoxin were not affected by treatment with tetrodotoxin (10(-6) M) and were observed even in the absence of external Na+. Furthermore, these effects were markedly inhibited or abolished by treatment with verapamil (30-300 microM), Mn2+ (5 mM), or tetracaine (1 mM). These results suggest that maitotoxin activates the voltage-dependent calcium channels of PC12h cells.

Adrenal Gland Neoplasms↗
PubMed1999

A sensitive and specific determination method for azaspiracids by liquid chromatography mass spectrometry.

A liquid chromatography/mass spectrometry (LC/MS) method was developed for the sensitive and specific determination of azaspiracid and its two analogs, the causative toxins of azaspiracid poisoning that occurred in the Netherlands and Ireland. The LC/MS method provided a detection limit of 50 pg for azaspiracid. The sensitivity was approximately 8 x 10(4) times greater than the mouse bioassay. The method was used to confirm the presence of azaspiracids in toxic mussels collected at Arranmore Island, Ireland in 1997.

Animals↗
PubMed2006

Maitotoxin potently promotes Ca2+ influx in mouse spermatogenic cells and sperm, and induces the acrosome reaction.

Maitotoxin (MTX), a potent marine toxin, activates Ca2+ entry via nonselective cation channels in a wide variety of cells. The identity of the channels involved in MTX action remains unknown. In mammalian sperm, Ca2+ entry through store-operated channels regulates a number of physiological events including the acrosome reaction (AR). Here we report that MTX produced an increase in the intracellular concentration of Ca2+ ([Ca2+]i) in spermatogenic cells that depended on extracellular Ca2+. Ni2+ and SKF96365 diminished the MTX-activated Ca2+ uptake, at concentrations they inhibit store-operated channels, and in a similar manner as they inhibit the Ca2+ influx activated following depletion of intracellular stores by thapsigargin (Tpg). In addition, MTX significantly increased [Ca2+]i in single mature sperm and effectively induced the AR with a half-maximal concentration (ED50) of approximately 1.1 nM. Notably, SKF96365 similarly inhibited the MTX-induced increase in sperm [Ca2+]i and the AR triggered by the toxin, Tpg and zona pellucida. These results suggest that putative MTX-activated channels may be involved in the Ca2+ influx required for mouse sperm AR.

Acrosome↗
PubMed1991

Dopamine receptor and adrenoceptor agonists inhibit prolactin release from MMQ cells.

MMQ cells, a prolactin-secreting cell line possessing dopamine receptors, were exposed to the calcium channel activator maitotoxin and dopamine or adrenoceptor agonists or antagonists. Dopamine (500 nM) or the dopamine agonists lisuride (50 nM), terguride (50 nM), and N-0437 (50 nM) decreased maitotoxin-stimulated prolactin release from perifused MMQ cells. In this system, sulpiride (100 nM), a dopamine D2 antagonist, reversed the prolactin inhibition produced by lisuride (20 nM). In static incubations of MMQ cells, lisuride (10-500 nM) inhibited maitotoxin-stimulated prolactin release in a concentration-dependent manner; this inhibition was attenuated in a concentration-related manner by sulpiride (100-500 nM). In addition, sulpiride reversed dopamine (50-500 nM), lisuride (10-500 nM), and terguride (50-500 nM) inhibition of forskolin-stimulated cAMP generation. The alpha 2-adrenergic agonist clonidine inhibited maitotoxin-stimulated prolactin release from perifused MMQ cells; this inhibition was abolished by idazoxan, an alpha 2-adrenergic antagonist. In contrast, serotonin or the serotonin antagonist methysergide had no effect on prolactin release from MMQ cells. These data indicate that activation of dopamine D2 receptors and alpha 2-adrenoceptors by classically defined pharmacological agents inhibits prolactin release and cellular cAMP levels in MMQ cells. Therefore, MMQ cells may provide a valuable model for the development of pharmacological agents and assist in the identification of the mechanisms involved in the dopaminergic inhibition of prolactin release.

Adrenergic Agonists↗
PubMed1990

Effects of maitotoxin on atrial natriuretic factor-mediated accumulation of cyclic GMP in PC12 cells.

Maitotoxin (MTX) activates calcium channels and stimulates phosphoinositide breakdown in pheochromocytoma PC12 cells, while having no effect on basal levels of the cyclic nucleotides cAMP and cGMP. Atrial natriuretic factor (ANF) induces a dose-dependent accumulation of cGMP in PC12 cells through the activation of a membrane bound guanylate cyclase. Effects of ANF on cGMP are independent of extracellular concentrations of calcium. Since agents that activate phosphoinositide breakdown can indirectly affect cyclic nucleotide formation, the effects of MTX on ANF-mediated accumulation of cGMP was studied. MTX induces a dose-dependent inhibition of ANF-mediated accumulation of cGMP. The inhibition by MTX requires the presence of extracellular calcium, but is unaffected by the calcium channel blocker nifedipine. The inhibitory effect of MTX is not mimicked by the calcium ionophore ionomycin. A phorbol ester, PMA, which stimulates protein kinase C, also inhibits ANF-mediated accumulation of cGMP. Sodium nitroprusside induces large accumulations of cGMP in PC12 cells through the stimulation of a soluble guanylate cyclase. Neither MTX nor PMA inhibit nitroprusside-mediated accumulation of cGMP. The results indicate that in PC12 cells, protein kinase C activation, either directly with PMA, and indirectly with MTX through phosphoinositide breakdown and formation of diacylglycerol, leads to inhibition of ANF-mediated, but not nitroprusside-mediated accumulation of cGMP.

Atrial Natriuretic Factor↗
PubMed1989

Cardiorespiratory effects of brevetoxin (PbTx-2) in conscious, tethered rats.

The cardiorespiratory effects of various doses of brevetoxin (0-100 micrograms PbTx-2/kg) were studied in conscious, tethered rats, After surgical preparation and a 24 hr recovery, toxin or vehicle was infused into the tethered, awake rats for 1 hr. They were then monitored for 6 hr or until death. Toxin-infused rats had decreased core and peripheral temperatures and decreased respiratory rates; these values were all low in the 100 micrograms/kg group at the time of death. Blood gas values remained within normal limits, except terminally. Electrocardiographic (ECG) disturbances, noted in all groups given greater than or equal to 25 micrograms/kg, included heart block, premature ventricular contractions and idioventricular rhythms. It was concluded that brevetoxin causes changes in cardiac conduction and multiple changes in nervous system function.

Animals↗
PubMed1990

Effect of maitotoxin on calcium current and background inward current in isolated ventricular rat myocytes.

Maitotoxin (MTX) irreversibly suppressed the voltage-dependent calcium current after a variable delay, an effect which was preceded, in 61% of the cells, by a transient increase in calcium current partly attributable to a shift (4-7 mV) of the activation curve towards negative potentials. MTX also induced the development of a voltage-independent background inward current which did not occur in the absence of external calcium and was reduced by removal of external sodium, by calcium channel blockers and by high concentrations of quinidine. MTX-induced single channel activity consisted of long lasting bursts of inward current. Channel activity was voltage-independent, with a unitary conductance of 14 pS and an extrapolated reversal potential of +16 mV. Single-channel current amplitude was not detectably reduced in the absence of external calcium but strongly reduced in the absence of external sodium, in the presence of 2 mM nickel or when external sodium was replaced by 96 mM calcium or 50 mM barium. The channel activity was also inhibited by quinidine. It is concluded that MTX alters, then suppresses the voltage-activated calcium current and induces the development of a voltage-independent inward current, part of which results from the opening of nickel-sensitive cation channels, mostly permeable to sodium ions.

Animals↗
PubMed1991

Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide.

The penetration and distribution of [3H]PbTx-3 into pig skin was determined using in vivo and in vitro methods. The dose used in each topical study was 0.3-0.4 micrograms/cm2 skin, with dimethylsulfoxide as the vehicle. In the in vivo study, mean cutaneous absorption after 48 h (expressed as percentage of the dose) was 11.5% (n = 3). In the in vitro study, mean cutaneous absorption after 48 h was 1.6% (n = 12), when based on accumulation of radioactivity in receptor fluid, or 9.9% when based on receptor fluid and dermis. [3H]PbTx-3 readily penetrated through the epidermis into the dermis, reaching maximal dermal accumulation at 4 h (9.1% in vivo and 18% in vitro). At 24 h, the amount in the dermis decreased to 2.3% and 15% in vivo and in vitro, respectively and at 48 h the amount in the dermis decreased to 8.2% in vitro. These results demonstrate the important role of the dermis as a reservoir for a lipophilic compound in both in vivo and in vitro percutaneous absorption studies.

Administration, Topical↗
PubMed1993

Ca(2+)- and Na(+)-dependent depolarization induced by maitotoxin in the crayfish giant axon.

1. Maitotoxin (MTX) depolarized the membrane of the crayfish giant axon and decreased the amplitude and maximum rate of rise of action potentials in an irreversible manner. 2. The depolarizing action of MTX was attenuated in low Ca (1 mM; 1/10 of normal concentration) solution and was also inhibited by 2 mM Co2+, 300 microM Ni/+, 1 microM nifedipine, 10 microM verapamil or 1 microM tetrodotoxin. 3. These results suggest that the depolarization by MTX in the crayfish giant axon may be related to changes not only in Ca permeability but also in Na permeability, possibly through the modification of existing Na or Ca channels and/or a new type of channel or pore induced by MTX.

Action Potentials↗
PubMed1992

Eutrophication, marine biotoxins, human health.

Eutrophication phenomena in marine coastal waters can today be explained on the basis of natural or anthropogenic causes. Undesirable effects and also sanitary problems in both types of eutrophication are often produced, but they may differ greatly in frequency and significance. Some algal biotoxins can affect both marine animals and man, whilst others affect man alone. From data currently available it appears that the sanitary state of man can be affected through the digestive, respiratory and cutaneous apparatus. Four main dinoflagellate biointoxications are now recognized: paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), diarrhoetic shellfish poisoning (DSP), and venerupin poisoning. Other biointoxications are due to a diatom bloom responsible for amnesic shellfish poisoning (ASP) and to blue algae blooms which have effects on the skin and the respiratory tract. All these marine toxins are considered and particular attention is paid to: producing organisms, chemistry of the components, compromised sea foods, methods of analysis, occurrence worldwide, human intoxications, toxicology and mechanism of action on a molecular level, therapeutical notes, tolerance levels and remarks on safety. Attention is also paid to the relationship between the anthropogenic eutrophication and PSP and DSP since these are the most widespread biointoxications from toxic marine dinoflagellates in the world today and for which the European Economic Community (EEC) is proposing health legislation such as tolerance limits and methods for official analysis. In view of the harmful potential of coastal anthropogenic eutrophication, the main current committment of various countries concerns control. Finally, it is important to develop a suitable monitor research system using all the specific standards of allowed toxic substances, and also research on effective antiodotes against all biotoxins.

Animals↗
PubMed2006

Differential dynamics of dinophysistoxins and pectenotoxins, part II: offshore bivalve species.

Different dinophysistoxin's profiles have been found repeatedly amongst some offshore bivalve molluscs. Species such as the clam, Spisula solida, esterify dinophysistoxins to a great extent, and contain always more okadaic acid (OA) than dinophysistoxin-2 (DTX2). In contrast, the clam Donax trunculus has a much higher percentage of non-esterified toxins, and often contains more DTX2 than OA. A detoxification experiment with D. trunculus and S. solida showed that the higher percentage of DTX2 in Donax was due to this toxin being eliminated more slowly than OA. The ester analogues of OA and DTX2 were eliminated faster than free OA and free DTX2 in D. trunculus. As D. trunculus esterifies OA to a greater extent than DTX2, the greater proportion of the free form of DTX2 explains why there is a gradual increase in total DTX2 over time. This slow elimination of free toxins contributes to wild D. trunculus specimens being, on average, six times more toxic than S. solida specimens on the Portuguese south coast. The commercial shellfish species more often monitored along the coast of Portugal between 2003 and 2004 (eight species in total) were examined for DTX2 content. The maximal percentage of total DTX2 in the total DSP toxins (OA + DTX2) was 40% in all species (clams, razors, cockles, oysters) except D. trunculus and Mytilus galloprovinciallis, in which it reached 70-90%. This phenomenon is seen only when contamination is due to the microalga Dinophysis acuta. The other important DSP-producer, Dinophysis acuminata, causes contamination only with OA. Current data suggest that D. acuta along the Portuguese coast always produces OA and DTX2 in a fixed ratio of 60:40. When this alga is dominant, contamination of bivalves occurs in a OA/DTX2 ratio of 60:40. In bivalves in which these toxins are esterified to a great extent, this profile is maintained due to the parallel elimination of OA and DTX2 esters at similar rates. However, in species with lower esterification, the relative proportion of OA and DTX2 rapidly decreases due to the selective retention of free DTX2. Elimination of pectenotoxin-2 seco acids (PTX2sa), the main pectenotoxin form found in both offshore species studied, followed an exponential decay. The half-lives of PTX2sas found in D. trunculus and S. solida were similar to that found in a previous study with the cockle, Cerastoderma edule, but longer than found in the blue mussel M. galloprovinciallis.

Animals↗