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Brevetoxin binding

Brevetoxins bind with high specificity to synaptosomes of fish (TUapia sp.)y turtles (P. scripta), and rats (Table I). In all cases, the K j was in the nanomolar... [Pg.168]

Huang et al. (7) suggested that the brevetoxin binding site lies in the hydro-phobic portion of the channel, and since PbTx-1 and PbTx-7 are also the most hydrophobic of the toxins, their potency may also be in part due to solubility considerations. In general, the more hydrophobic the toxin, the higher is its potency and ability to displace tritiated PbTx-3 from its specific binding site. It is our contention that substituent character on each toxin s K (type-1) or J (type-2) ring... [Pg.173]

Figure 2.3. The brevenals are shorter transfused polyether molecules isolated from K. brevis. Consisting of a 6-7-6-7-7 ring motif, these materials bind with high affinity in brevetoxin receptor assays, and effectively act as inhibitors of brevetoxin binding and activity. Brevenal is the major constituent derived from cultures or the environment, with smaller amounts of brevenol (brevenal with the aldehyde reduced to the alcohol) (Baden et al. 2005). Figure 2.3. The brevenals are shorter transfused polyether molecules isolated from K. brevis. Consisting of a 6-7-6-7-7 ring motif, these materials bind with high affinity in brevetoxin receptor assays, and effectively act as inhibitors of brevetoxin binding and activity. Brevenal is the major constituent derived from cultures or the environment, with smaller amounts of brevenol (brevenal with the aldehyde reduced to the alcohol) (Baden et al. 2005).
Inoue, M., Hirama, M., Satake, M., Sugiyama, K., and Yasumoto, T. 2003. Inhibition of brevetoxin binding to the voltagegated sodium channel by gambierol and gambieric acid-A. Toxicon 41, 469-474. [Pg.44]

Yuhi, T., et al.. Characterization of [3H]brevetoxin binding to voltage-dependent sodium channels in adrenal medullary cells. Naunyn Schmiedebergs Arch Pharmacol, 1994 350(2) 209-212. [Pg.515]

Edwards, R.A., Stuart, A.M. and Baden, D.G., Brevetoxin binding in three phylogenetically diverse... [Pg.557]

Ciguatoxins, same as brevetoxins, bind to site 5 on sodium channels, so toxins can be detected based on their ability to selectively inhibit the binding of [ H]-brevetoxin to sodium channels in rat brain synaptosomes. ° Inoue et al. published that gambierol was able to displace [ H] -brevetoxin from its binding site in the same conditions as ciguatoxins, though at higher concentration. ... [Pg.620]

Brevetoxins bind with high affinity to site 5 of the voltage-sensitive sodiiun channel (VSSC) in neurons, causing the chaimel to remain in the open state and inhibit channel inactivation, thus prolonging the duration of sodiiun currents across the membrane [7]. [Pg.36]

Stabilizers bind at a site separate from those of traditional activators and of ciguatoxin-brevetoxin, but they exert a synergistic action on both types of activators (J5, 42). This action potentiates the activators and generally increases their efficacy, yielding larger depolarizations at lower doses 42) it occurs uniquely with the peptide stabilizers and not with ions or oxidants that also slow the inactivation of Na current 37). [Pg.12]

Figure 8. A schematic for the toxin binding sites on the voltage-gated Na channel. Toxin-free open and closed conformations are drawn at the left and center. Separate sites are depicted within the membrane for activators such as BTX, VTD (A), and brevetoxin (B) these are coupled to each other and to the a-peptide toxin site (a), which is kinetically linked to the -peptide toxin site (P see ref. 20). Near the outer opening of the pore is a site (G) for STX and TTX which is affected by binding at site A and which can modify inactivation gating. Figure 8. A schematic for the toxin binding sites on the voltage-gated Na channel. Toxin-free open and closed conformations are drawn at the left and center. Separate sites are depicted within the membrane for activators such as BTX, VTD (A), and brevetoxin (B) these are coupled to each other and to the a-peptide toxin site (a), which is kinetically linked to the -peptide toxin site (P see ref. 20). Near the outer opening of the pore is a site (G) for STX and TTX which is affected by binding at site A and which can modify inactivation gating.
Dissociation Constants and Binding Maxima for Brevetoxin PbTx-3... [Pg.168]

Figure 6. Effect of brevetoxins on tritiated PbTx-3 binding to rat brain synaptosomes. Incubations, in the presence of 50 fig synaptosomal protein and 16 nM tritiated PbTx-3 with increasing amounts of unlabeled PbTx-1 ( ), PbTx-2 ( ), PbTx-3 ( ), PbTx-5 (A), PbTx-6 ( ), or PbTx-7 (o) were for 1 hr at 4 C. Each point represents the mean of three triplicate determinations. Figure 6. Effect of brevetoxins on tritiated PbTx-3 binding to rat brain synaptosomes. Incubations, in the presence of 50 fig synaptosomal protein and 16 nM tritiated PbTx-3 with increasing amounts of unlabeled PbTx-1 ( ), PbTx-2 ( ), PbTx-3 ( ), PbTx-5 (A), PbTx-6 ( ), or PbTx-7 (o) were for 1 hr at 4 C. Each point represents the mean of three triplicate determinations.
Table II. Speciflc Displacement of [hi] PbTx-3 Dx)m Synaptosome Binding by Unlal led Brevetoxins, Comparison with LD ... Table II. Speciflc Displacement of [hi] PbTx-3 Dx)m Synaptosome Binding by Unlal led Brevetoxins, Comparison with LD ...
K, which necessitates use of high specific activity radioactive toxin (at or above 10 Ci/mmol). Work in progress indicates that all type-1 brevetoxins inhibit tritiated PbTx-3 binding in a purely competitive manner, whereas the type-2 brevetoxins inhibit in a mixed competition manner at higher concentrations (Figure 7). [Pg.173]

The comparison of fish bioassays (6) with the calculated effective doses indicate that the two most potent brevetoxins, PbTx-1 and PbTx-7, also are most effective at displacing tritiated probe from its specific site of action. The considerably lower potency of brevetoxins PbTx-5 and PbTx-6 in the rat system suggest that these two toxins may bind with lesser affinity to site 5. In a general sense, this is indicated in Table II, and is summmarized in Table III. [Pg.173]

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... [Pg.176]

After initial experiments demonstrating that the antiserum was capable of completely inhibiting the binding of [ H]PbTx-3 to its receptor site in rat brain membranes (Figure 9), we began studies designed to evaluate potential of the antiserum for prophylaxis and treatment of brevetoxin intoxication (34). The tethered rat model was used, and surgical implantations were identical to those described above. Heart rate, core and peripheral body temperatures, lead VIO ECG, and arterial blood pressure were monitored continuously. Respiratory rate was recorded each 5 min for the first 3 hr, then each 15 min until 6 hr. [Pg.187]


See other pages where Brevetoxin binding is mentioned: [Pg.168]    [Pg.171]    [Pg.171]    [Pg.173]    [Pg.365]    [Pg.300]    [Pg.531]    [Pg.532]    [Pg.535]    [Pg.539]    [Pg.168]    [Pg.171]    [Pg.171]    [Pg.173]    [Pg.365]    [Pg.300]    [Pg.531]    [Pg.532]    [Pg.535]    [Pg.539]    [Pg.732]    [Pg.7]    [Pg.15]    [Pg.15]    [Pg.146]    [Pg.163]    [Pg.166]    [Pg.171]    [Pg.177]    [Pg.187]    [Pg.187]    [Pg.192]    [Pg.195]    [Pg.196]    [Pg.196]   
See also in sourсe #XX -- [ Pg.226 ]




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Brevetoxin

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