Agatoxin - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

Agatoxin

The Experts below are selected from a list of 3015 Experts worldwide ranked by ideXlab platform

Agatoxin – Free Register to Access Experts & Abstracts

Kurt M. Howse – One of the best experts on this subject based on the ideXlab platform.

  • ω-Agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism
    European journal of pharmacology, 1996
    Co-Authors: Sandra C. Roerig, Kurt M. Howse

    Abstract:

    Abstract Involvement of P-type voltage-dependent Ca2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-Agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-Agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-Agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-Agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.

  • ω Agatoxin iva blocks spinal morphine clonidine antinociceptive synergism
    European Journal of Pharmacology, 1996
    Co-Authors: Sandra C. Roerig, Kurt M. Howse

    Abstract:

    Abstract Involvement of P-type voltage-dependent Ca2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-Agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-Agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-Agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-Agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.

Michael E. Adams – One of the best experts on this subject based on the ideXlab platform.

  • Heterodimeric
    , 2013
    Co-Authors: Brian T. Chait, Michael E. Adams, John P. Hunspergers, Baldomero M. Oliveras, David R. Hillyard

    Abstract:

    We report the first molecular characterization of a precursor sequence for a small, Ca2+ channel blocking, peptide spider toxin, w-Agatoxin IA. By integrating information generated from a molecular genetic approach using Agatoxin cDNAs with data provided from mass spectrometry of the mature toxin, we were able to deduce the likely mechanisms by which the toxin precursor peptide is processed to its mature heterodimeric form. A particularly interesting feature of the prepropeptide is the occurrence of two glutamate-rich sequences interposed between the signal sequences, the major peptide toxin, and the minor toxin peptide. Excision of the more distal glutamate-rich region appears to be signaled by flanking arginine residues but likely occurs only after a disulfide linkage has formed betwee

  • Agatoxins: ion channel specific toxins from the American funnel web spider, Agelenopsis aperta.
    Toxicon : official journal of the International Society on Toxinology, 2004
    Co-Authors: Michael E. Adams

    Abstract:

    Agatoxins from Agelenopsis aperta venom target three classes of ion channels, including transmitter-activated cation channels, voltage-activated sodium channels, and voltage-activated calcium channels. The α-Agatoxins are non-competitive, use-dependent antagonists of glutamate receptor channels, and produce rapid but reversible paralysis in insect prey. Their actions are facilitated by the μ-Agatoxins, which shift voltage-dependent activation of neuronal sodium channels to more negative potentials, causing spontaneous transmitter release and repetitive action potentials. The ω-Agatoxins target neuronal calcium channels, modifying their properties in distinct ways, either through gating modification (ω-Aga-IVA) or by reduction of unitary current (ω-Aga-IIIA). The α-Agatoxins and ω-Agatoxins modify both insect and vertebrate ion channels, while the μ-Agatoxins are selective for insect channels. Agatoxins have been used as selective pharmacological probes for characterization of ion channels in the brain and heart, and have been evaluated as candidate biopesticides.

  • Three-dimensional structure analysis of mu-Agatoxins: further evidence for common motifs among neurotoxins with diverse ion channel specificities.
    Biochemistry, 1996
    Co-Authors: Diana O. Omecinsky, Michael E. Adams, Katherine E. Holub, Michael D. Reily

    Abstract:

    We report the solution structure of mu-Agatoxin-I (mu-Aga-I) and model structures of the closely related mu-Agatoxin-IV (mu-Aga-IV) which were isolated from venom of the American funnel web spider, Agelenopsis aperta. These toxins, which modify the kinetics of neuronal voltage-activated sodium channels in insects, are C-terminally amidated peptides composed to 36 amino acids, including four internal disulfide bonds. The structure of mu-Aga-I was determined by NMR and distance geometry/molecular dynamics calculations. Structural calculations were carried out using 256 interresidue NOE-derived distance restraints and 25 angle restraints obtained from vicinal coupling constants. The peptide contains eight cysteines involved in disulfide bonds, the pairings of which were uncertain and had to be determined from preliminary structure calculations. The toxin has an average rmsd of 0.89 A for the backbone atoms among 38 converged conformers. The structure consists of a well-defined triple-stranded beta-sheet involving residues 7-9, 20-24, and 30-34 and four tight turns. A homologous peptide, mu-Aga-IV, exhibited two distinct and equally populated conformations in solution, which complicated spectral analysis. Analysis of sequential NOE’s confirmed that the conformers arose from cis and trans peptide bonds involving a proline at position 15. Models were developed for both conformers based on the mu-Aga-I structure. Our structural data show that the mu-Agatoxins, although specific modifiers of sodium channels, share common secondary and tertiary structural motifs with phylogenetically diverse peptide toxins targeting a variety of channel types. The mu-Agatoxins add voltage-sensitive sodium channel activity to a growing list of neurotoxic effects elicited by peptide toxins which share the same global fold yet differ in their animal origin and ion channel selectivity.

Sandra C. Roerig – One of the best experts on this subject based on the ideXlab platform.

  • ω-Agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism
    European journal of pharmacology, 1996
    Co-Authors: Sandra C. Roerig, Kurt M. Howse

    Abstract:

    Abstract Involvement of P-type voltage-dependent Ca2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-Agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-Agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-Agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-Agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.

  • ω Agatoxin iva blocks spinal morphine clonidine antinociceptive synergism
    European Journal of Pharmacology, 1996
    Co-Authors: Sandra C. Roerig, Kurt M. Howse

    Abstract:

    Abstract Involvement of P-type voltage-dependent Ca2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-Agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-Agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-Agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-Agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.