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51.
S Asai J J Krzanowski R F Lockey W H Anderson D F Martin J B Polson S C Bukantz A Szentivanyi 《The Journal of allergy and clinical immunology》1984,73(6):824-828
The red tide toxin produced by Ptychodiscus brevis ( PBTX ) may cause cough, sneezing, and asthma. Previous in vitro studies with isolated canine tracheal smooth muscle demonstrated that PBTX stimulates sodium channels of parasympathetic nerve endings and thus causes a contractile response. The present study investigated the mechanism of the PBTX effect on canine tracheal smooth muscle. Repeated exposure of the muscle strip to PBTX (final concentration 46 micrograms/ml) followed by washout of the toxin resulted in reestablishment of baseline tension but a failure of contraction on further addition of PBTX . However, veratridine and scorpion toxin (SCT), which are voltage-sensitive sodium channel activators, still induced contraction. Furthermore, the contraction caused by veratridine was enhanced by a high dose of PBTX , whereas contraction caused by SCT was not. Responses to veratridine and SCT as well as PBTX (previously reported) were blocked by tetrodotoxin (a sodium channel blocker), while acetylcholine responsiveness remained intact. These results indicate that PBTX receptors in parasympathetic nerves influence Na+ flux at the h gate, that these receptors differ from the veratridine and SCT receptors, and that the conformational change in the receptors induced by PBTX affects the tissue response to veratridine. 相似文献
52.
河南马氏钳蝎粗毒对体外培养的人食管癌细胞株(Eca109)的毒性 总被引:7,自引:0,他引:7
本文应用产于河南的马氏钳蝎(buthus martensii karshi)分泌的粗毒(scorpion venom crude,SVC)处理体外培养的人食管癌细胞株——Eca109,观察了SVC对Eca109细胞的生长抑制及细胞毒性作用。结果显示,SVC可以抑制Eca109细胞的生长,SVC的浓度为0.017μg/ml,处理细胞24、48、72hr后,细胞生长的抑制率达35.6%、39.5%、36.9%;SVC亦可抑制Eca109细胞线粒体脱氢酶的活性,对细胞呈现细胞毒性作用,SVC浓度为0.017μg/ml、0.034μg/ml、0.085μg/ml时,对Eca109细胞的细胞毒性作用分别达63%、56%、59%。SVC对肿瘤细胞的毒性作用及其作用机理值得深入研究。 相似文献
53.
Tityusγ toxin,a high affinity effector of the Na+ channel in muscle,with a selectivity for channels in the surface membrane 总被引:1,自引:0,他引:1
Jacques Barhanin Michèle Ildefonse Oger Rougier Suely Vilela Sampaio José R. Giglio Michel Lazdunski 《Pflügers Archiv : European journal of physiology》1984,400(1):22-27
Toxin from the venom ofTityus serrulatus scorpion produces a partial block of the surface Na+ channel in frog muscle. This block occurs with no change in the voltage-dependence or in the kinetics of the remaining surface Na+ current. The partial blockade of Na+ channel activity occurs with no change in tubular Na+ currents nor in twitch tension. The maximum effect of the toxin is attained at concentrations as low as 3×10–10 M. Hyperpolarization to potentials more negative than the resting potential (E=–90 mV) reduces or abolishes the effect of the toxin.Radioiodinated toxin binds to frog muscle membranes with a very high affinity corresponding to a dissociation constant of about 1×10–11 M. Data obtained with both rabbit and frog muscle indicate that toxin is specific for Na+ channels in surface membranes. Toxin does not seem to bind to Na+ channels in T-tubule membranes. The biochemical data are in good agreement with electrophysiological studies and data on contraction. There is oneTityus toxin binding site per tetrodotoxin binding site in surface membranes. Competition experiments have confirmed thatTityus toxin binds to a new toxin receptor site on the Na+ channel structure. This site is the same that the toxin II fromCentruroides suffusus binding site, but this toxin has 100 times less affinity for the Na+ channel thanTityus toxin. 相似文献
54.
[目的]总结吴玉生教授治疗肝癌的学术观点及临证经验,并在临床中进一步推广。 相似文献
55.
The cDNAs encoding nine novel α-toxin homologues were isolated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch (BmK). They are rich in AAAA and TTTT elements at the 5′ UTRs. The flanking region of the translation initiation codon ATG is AAAATGAA, which is highly conserved in scorpion Na+, K+ and Cl− channel toxin genes. These putative scorpion α-toxins shared 45.5–98.4% homology with the characterized BmK α-toxins, and were completely conserved in the positions of all eight cysteines. This showed, together with higher homology at nucleotide level than that at amino acid level, that these toxins may originate from a common ancestor. The discovery of a series of homologues of scorpion α-toxin with a different degree of natural mutation in the primary structure will provide us with a valuable system for studying the structure–function relationship of scorpion toxins. 相似文献
56.
57.
Song Han Youtian Hu Ruhong ZhangHong Yi Jingjing WeiYingliang Wu Zhijian CaoWenxin Li Xiaohua He 《Toxicon》2011,57(2):348-355
Scorpion toxins are useful in the structure-function research of ion channels and valuable resources for drug design. The Kv1.3 channel is an important pharmacological target for the therapy of T cell-mediated autoimmune diseases, and many toxin peptides targeting Kv1.3 have been identified as good drug candidates in recent years. In this study, a novel toxin gene ImKTx88 was isolated from the venom of the scorpion Isometrus maculates through the construction of the cDNA library method, and the recombinant toxin peptide was purified and characterized physiologically. The mature peptide of ImKTx88 contained 39 amino acid residues including six cysteines and was predicted to be a new member of α-KTx scorpion family by sequence analysis. The electrophysiological experiments further indicated that the rImKTx88 peptide had a novel pharmacological profile: it inhibited Kv1.3 channel current with an IC50 of 91 ± 42 pM, and exhibited very good selectivity for Kv1.3 over Kv1.1 (4200-fold) and Kv1.2 (93000-fold) channels, respectively. All these results suggested that, as a new selective Kv1.3 channel blocker, the ImKTx88 peptide may serve as a potential drug candidate in the therapy of autoimmune diseases. 相似文献
58.
C.T. ColognaS. Peigneur J.C. RosaH.S. Selistre-de-Araujo W.A. VarandaJ. Tytgat E.C. Arantes 《Toxicon》2011,58(1):54-61
Voltage-gated potassium channel toxins (KTxs) are basic short chain peptides comprising 23-43 amino acid residues that can be cross-linked by 3 or 4 disulfide bridges. KTxs are classified into four large families: α-, β-, γ- and κ-KTx. These peptides display varying selectivity and affinity for Kv channel subtypes. In this work, a novel toxin from the Tityus serrulatus venom was isolated, characterized and submitted to a wide electrophysiological screening on 5 different subtypes of NaV channels (NaV1.4; NaV1.5; NaV1.6; NaV1.8 and DmNaV1) and 12 different subtypes of KV channels (KV1.1 - KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; Shaker IR and ERG). This novel peptide, named Ts15, has 36 amino acids, is cross-linked by 3 disulfide bridges, has a molecular mass of 3956 Da and pI around 9. Electrophysiological experiments using patch clamp and the two-electrode voltage clamp techniques show that Ts15 preferentially blocks KV1.2 and KV1.3 channels with an IC50 value of 196 ± 25 and 508 ± 67 nM, respectively. No effect on NaV channels was observed, at all tested concentrations. Since Ts15 shows low amino acid identity with other known KTxs, it was considered a bona fide novel type of scorpion toxin. Ts15 is the unique member of the new α-Ktx21 subfamily and therefore was classified as α-Ktx21.1. 相似文献
59.
Zayerzadeh E Koohi MK Mirakabadi AZ Fardipoor A Kassaian SE Rabbani S Anvari MS 《Toxicon》2012,59(2):249-256
Immunotherapy is the only specific treatment for scorpion sting. In the present study, protective effects of polyvalent antivenom against hemodynamic disturbances, biomarkers (troponin T, creatinine kinase isoenzyme MB, Lactate dehydrogenase) changes, electrocardiogram abnormalities and histopathological complications in heart and lung induced by Mesobuthus eupeus scorpion venom was investigated in anesthetized rabbits. Twenty four rabbits were randomized into four equal groups: six rabbits in control group received 1 ml ultra-pure water subcutaneously (group 1). Group two received LD50 of venom (4.5 mg/kg). In the third and fourth groups, 5 ml of scorpion antivenom was administrated intravenously simultaneous with venom injection and 60 min following envenomation, respectively. Results of the present study indicate significant decrease in hemodynamic parameters following envenomation in the second group of animals. Venom injection caused edema, myocytolysis, coagulation necrosis, hemorrhage in heart as well as edema, hemorrhage and vascular thrombus in lungs. Although envenomed rabbits presented rises in LDH and TnT but no alteration in CK-MB was observed. Electrocardiogram monitoring of rabbits showed ST elevation and inverted T waves. Simultaneous administration of antivenom and venom prevented entirely the clinical signs, hemodynamic disturbances, markers changes, ECG abnormalities and histopathological damages. Delayed immunotherapy gradually ameliorated clinical signs, hemodynamic disturbances and markers changes related to envenomation. Histopathological evaluation showed slight alterations such as mild myocytolysis in heart and mild edema in lung following delayed immunotherapy. In conclusion, scorpion antivenom administration has preventive, neutralizing and curative properties for M. eupeus scorpion envenomation, if it would be applied at optimum time, dose and route. 相似文献
60.
Scorpion venoms are rich sources of bioactive peptides and are widely known for their ion channel inhibiting properties. We have isolated, cloned and characterized a venom protein (Bumarsin) from the Chinese scorpion, Mesobuthus martensii Karsch. Bumarsin cDNA encodes a 8132 Da, 72 amino acid mature protein that most probably exists in its native form as a Cys-bridged homodimer. We have identified this novel protein to be an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity. 0.6 μM of Bumarsin inhibits 32% of the HMG-CoA reductase activity, in comparison to 10 μM simvastatin which only inhibits 35% of the activity. RT-PCR and SELDI-TOF mass spectrometric studies demonstrate that bumarsin regulates the expression of both genes and proteins involved in cholesterol homeostasis. Our results suggest that bumarsin may provide a model for the design of novel drugs that can be used to modulate cholesterol homeostasis. 相似文献