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Every cone snail produces a mixture of different conotoxins and secretes them to immobilize their prey and predators. α3/5 Conotoxins, isolated from fish-hunting cone snails, target muscle nicotinic acetylcholine receptors. The structure and function of α3/5 conotoxin from the piscivorous Conus achatinus have not been studied. We synthesized two pentadecamer peptides, Ac 1.1 a and Ac 1.1 b, with appropriate disulfide bonding, based on cDNA sequences of α3/5 conotoxins from C. achatinus. Ac 1.1 a and Ac 1.1 b differ by only one amino acid residue. They have similar potency on blocking recombinant mouse muscle acetylcholine receptor expressed in Xenopus laevis oocytes, with IC50values of 36 nM and 26 nM, respectively. For Ac 1.1b, deletion of the first three N-terminal amino acids did not change its activity, indicating that the Nterminus is not involved in the interaction with its receptor. Furthermore, our experiments indicate that both toxins strongly prefer the α1-δ subunit interface instead of the α1-γ binding site on the mouse muscle nicotinic acetylcholine receptor. These peptides provide additional tools for the study of the structure and function of nicotinic receptor.

关键词： cone snail α3/5 conotoxin disulfide bond nicotinic acetylcholine receptor

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Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as novel antagonists of nicotinic acetylcholine receptors

Characterization of two α4/7-conotoxins,Mrl.1 and Lpl.4,as ...

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第九届中国生物毒素学术研讨会

作者： Tanya Sanders Geoffrey Chew edward Hawrot Department of Molecular Pharmacology.Physiology and Biotechnology Brown Medical SchoolProvidenceRhode Island 02912USA

＜正＞α-Conotoxins from cone snails are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors（nAChRs）.We recently identified two conopeptides in venom duct mRNA and muscle tissue genomic DNA from the South China Sea species,Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus *** have the typical 4/7-type framework characteristic of the subfamily ofα-conotoxins that act on neuronal-type *** two toxins were chemically synthesized and folded into the globular disulfide isomer through different oxidative approaches. Functional studies were carried out in oocytes expressing various nAChRs and with a rat model of inflammatory *** synthetic Mr1.1 primarily inhibited ACh-evoked currents reversibly in the ratα7 receptor,whereas Lp1.4 s unexpectedly a specific blocker of the mouse fetal muscleα1β1γδ*** the two toxins share low-affinity inhibition of nAChRs at high toxin concentrations,their unique receptor recognition profiles make them valuable tools for studying the toxin-receptor *** 1.1 was also shown to potently suppress the inflammatory response to pain in vivo,suggesting that it should be further investigated with respect to the molecular role of Mr1.1 in analgesia and its mechanism or therapeutic target for the treatment of pain.

关键词： Conus α4/7-conotoxins nicotinic acetylcholine receptors analgesia

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Usefulness of intra-procedural cone-beam computed tomography in modified balloon-occluded retrograde transvenous obliteration of gastric varices

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World Journal of Radiology 2016年第4期8卷 390-396页

作者： edward Wolfgang Lee Naomi So Ryan Chapman Justin P McWilliams Christopher T Loh Ronald W Busuttil Stephen T Kee Division of Interventional Radiology Department of RadiologyUCLA Medical CenterDavid Geffen School of Medicine at UCLA Dumont-UCLA Transplant Center Pfleger Liver InstituteDivision of Liver and Pancreas TransplantationDepartment of SurgeryDavid Geffen School of Medicine at University of California

AIM:To evaluate whether intra-procedural conebeam computed tomography(CBCT)performed during modified balloon-occluded retrograde transvenous obliteration(mB RTO)can accurately determine technical success of complete variceal ***:From June 2012 to December 2014,15 patients who received CBCT during m BRTO for treatment of portal hypertensive gastric variceal bleeding were retrospectively ***-dimensional(3D)CBCT images were performed and evaluated prior to the end of the procedure,and these were further analyzed and compared to the pre-procedure contrast-enhanced computed tomography to determine the technical success of m BRTO including:Complete occlusion/obliteration of:(1)gastrorenal shunt(GRS);(2)gastric varices;and(3)afferent feeding ***-mB RTO contrast-enhanced CT was used to confirm the accuracy and diagnostic value of CBCT within 2-3 ***:Intra-procedural 3D-CBCT images were 100% accurate in determining the technical success of m BRTO in all 15 *** demonstrated complete occlusion/obliteration of GRS,gastric varices,collaterals and afferent feeding veins during m BRTO,which was confirmed with post-m BRTO *** patients showed incomplete obliteration of gastric varices and feeding veins on CBCT,which therefore required additional gelfoam injections to complete the *** patient required additional procedures or other interventions during their follow-up period(684 ± 279 d).CONCLUSION:CBCT during mB RTO appears to accurately and immediately determine the technical success of mB *** may improve the technical and clinical success/outcome of m BRTO and reduce additional procedure time in the future.

关键词： Gastric varices Modified balloon-occluded retrograde transvenous obliteration Gastric variceal bleeding cone-beam computed tomography Coilassisted retrograde transvenous obliteration

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