omega conotoxins

Summary

Summary: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.

Top Publications

  1. Fujita Y, Mynlieff M, Dirksen R, Kim M, Niidome T, Nakai J, et al. Primary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brain. Neuron. 1993;10:585-98 pubmed
    ..Cell-attached patch recordings, with isotonic barium as the charge carrier, revealed distinct single channels with an average slope conductance of 14.3 pS. ..
  2. Xia Z, Chen Y, Zhu Y, Wang F, Xu X, Zhan J. Recombinant omega-conotoxin MVIIA possesses strong analgesic activity. BioDrugs. 2006;20:275-81 pubmed
    ..The analgesic activity of the conotoxin was about 800 times stronger than that of morphine. The recombinant CTX MVIIA expressed in E. coli has shown marked analgesic activity, which may have potential in clinical application. ..
  3. Miljanich G. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem. 2004;11:3029-40 pubmed
    ..If approved for clinical use, ziconotide will further validate the neuroactive venom peptides as a source of new and useful medicines. ..
  4. Wang Y, Pettus M, Gao D, Phillips C, Scott Bowersox S. Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain. Pain. 2000;84:151-8 pubmed
    ..The results of this study show that intrathecal ziconotide is antinociceptive in a rat incisional model of post-operative pain and is more potent, longer acting, and more specific in its actions than intrathecal morphine. ..
  5. Staats P, Yearwood T, Charapata S, Presley R, Wallace M, Byas Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291:63-70 pubmed
    ..5% of those receiving placebo (P =.001). Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS. ..
  6. Pinheiro A, da Silva A, Prado M, Cordeiro M, Richardson M, Batista M, et al. Phoneutria spider toxins block ischemia-induced glutamate release, neuronal death, and loss of neurotransmission in hippocampus. Hippocampus. 2009;19:1123-9 pubmed publisher
    ..Thus Tx3-3 and Tx3-4 provided robust ischemic neuroprotection showing potential as a novel class of agent that exerts neuroprotection in an in vitro model of brain ischemia. ..
  7. Glassmeier G, Hauber M, Wulfsen I, Weinsberg F, Bauer C, Schwarz J. Ca2+ channels in clonal rat anterior pituitary cells (GH3/B6). Pflugers Arch. 2001;442:577-87 pubmed
    ..Blockage of L-type channels with 10 microM nifedipine or P/Q-type channels with 10 nM omega-agatoxin MVIIC + 200 nM omega-conotoxin blocked action potential firing in GH3/B6 cells and decreased basal prolactin secretion. ..
  8. Ryan S, Shotts L, Hong S, Nehra D, Groat C, Armstrong J, et al. Glutamate regulates neurite outgrowth of cultured descending brain neurons from larval lamprey. Dev Neurobiol. 2007;67:173-88 pubmed
    ..Signaling mechanisms involving intracellular calcium, similar to those shown here, may be important for regulating axonal regeneration following spinal cord injury in the lamprey. ..
  9. Bisschops R, Vanden Berghe P, Bellon E, Janssens J, Tack J. Electrical stimulation reveals complex neuronal input and activation patterns in single myenteric guinea pig ganglia. Am J Physiol Gastrointest Liver Physiol. 2003;284:G1084-92 pubmed
    ..We conclude that, at least for ETS close to a ganglion, confocal calcium imaging reveals complex oral and aboral input to individual myenteric neurons rather than a polarization in spread of activity. ..

More Information

Publications62

  1. Sluka K. Blockade of N- and P/Q-type calcium channels reduces the secondary heat hyperalgesia induced by acute inflammation. J Pharmacol Exp Ther. 1998;287:232-7 pubmed
    ..Thus, N-type calcium channels contribute to both the development and maintenance of secondary heat hyperalgesia while P-type calcium channels are only involved during development of hyperalgesia. ..
  2. Bonicalzi V, Canavero S. Intrathecal ziconotide for chronic pain. JAMA. 2004;292:1681-2; author reply 1682 pubmed
  3. Isaacson J. Mechanisms governing dendritic gamma-aminobutyric acid (GABA) release in the rat olfactory bulb. Proc Natl Acad Sci U S A. 2001;98:337-42 pubmed
    ..These results indicate that voltage-gated calcium channels play an essential role in dendritic GABA release during reciprocal feedback inhibition in the olfactory bulb. ..
  4. Montero M, Alonso M, Albillos A, Cuchillo Ibanez I, Olivares R, G GarcĂ­a A, et al. Control of secretion by mitochondria depends on the size of the local [Ca2+] after chromaffin cell stimulation. Eur J Neurosci. 2001;13:2247-54 pubmed
    ..By contrast, Ca2+ entry through P/Q-type channels fully activated mitochondrial Ca2+ uptake. Control of secretion by mitochondria therefore depends critically on the ability of the stimulus to create large local [Ca2+]c microdomains. ..
  5. Matsuda T, Shimizu I, Baba A. Na+ influx-induced decrease of (Na+ + K+)-ATPase activity in rat brain slices: role of Ca2+. Eur J Pharmacol. 1991;204:257-63 pubmed
    ..Dithiothreitol (10 mM) blocked the effect of monensin on enzyme activity but did not affect the ionophore-induced influx of Ca2+ in the slices. ..
  6. Triguero D, Gonzalez M, Garcia Pascual A, Costa G. Atypical relaxation by scorpion venom in the lamb urethral smooth muscle involves both NO-dependent and -independent responses. Naunyn Schmiedebergs Arch Pharmacol. 2003;368:151-9 pubmed
    ..In addition, the likely involvement of CNGCs as an additional component of the cGMP signalling mechanism is suggested. ..
  7. Prommer E. Ziconotide: can we use it in palliative care?. Am J Hosp Palliat Care. 2005;22:369-74 pubmed
    ..Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs. Ziconotide may represent another option for patients with refractory pain. ..
  8. Pardo N, Hajela R, Atchison W. Acetylcholine release at neuromuscular junctions of adult tottering mice is controlled by N-(cav2.2) and R-type (cav2.3) but not L-type (cav1.2) Ca2+ channels. J Pharmacol Exp Ther. 2006;319:1009-20 pubmed
    ..However, it is unclear which conditions underlie recruitment of Ca(v)2 as opposed to Ca(v)1-type Ca(2+) channels. ..
  9. Gowd K, Dewan K, Iengar P, Krishnan K, Balaram P. Probing peptide libraries from Conus achatinus using mass spectrometry and cDNA sequencing: identification of delta and omega-conotoxins. J Mass Spectrom. 2008;43:791-805 pubmed publisher
    ..Crude venom analysis should prove powerful in studying both inter- and intra-species variation in peptide libraries. ..
  10. Rauck R, Wallace M, Burton A, Kapural L, North J. Intrathecal ziconotide for neuropathic pain: a review. Pain Pract. 2009;9:327-37 pubmed publisher
    ..Additional studies are needed to establish the long-term efficacy and safety of ziconotide for neuropathic pain. ..
  11. Bennett M, Kerr R, Khurana G. Adenosine modulation of calcium currents in postganglionic neurones of avian cultured ciliary ganglia. Br J Pharmacol. 1992;106:25-32 pubmed
    ..7. These observations of the effects of 2-chloroadenosine on the transient and sustained currents are discussed in relation to the different calcium channel types at preganglionic nerve terminals. ..
  12. Kelly K, Kume A, Albin R, Macdonald R. Autoradiography of L-type and N-type calcium channels in aged rat hippocampus, entorhinal cortex, and neocortex. Neurobiol Aging. 2001;22:17-23 pubmed
  13. Feng Z, Hamid J, Doering C, Bosey G, Snutch T, Zamponi G. Residue Gly1326 of the N-type calcium channel alpha 1B subunit controls reversibility of omega-conotoxin GVIA and MVIIA block. J Biol Chem. 2001;276:15728-35 pubmed
  14. De la Fuente M, Maroto R, Esquerro E, Sanchez Garcia P, Garcia A. The actions of ouabain and lithium chloride on cytosolic Ca2+ in single chromaffin cells. Eur J Pharmacol. 1996;306:219-26 pubmed
    ..Through its binding to the Na+ site on the Na(+)-Ca2+ exchanger, Li+ ions generate powerful Cai2+ signals that might be relevant to its known effects on neurosecretory mechanisms. ..
  15. Waterman S. Multiple subtypes of voltage-gated calcium channel mediate transmitter release from parasympathetic neurons in the mouse bladder. J Neurosci. 1996;16:4155-61 pubmed
    ..Furthermore, the release of the two main transmitters in these neurons has differing dependencies on the calcium channel subtypes. ..
  16. Fletcher C, Tottene A, Lennon V, Wilson S, Dubel S, Paylor R, et al. Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity. FASEB J. 2001;15:1288-90 pubmed
  17. Bossu J, De Waard M, Feltz A. Two types of calcium channels are expressed in adult bovine chromaffin cells. J Physiol. 1991;437:621-34 pubmed
    ..By contrast, L-type currents recorded in the whole-cell configuration are always observed and are insensitive to Bay K 8644. These results indicate that L-type channels are normally inoperable in chromaffin cells. ..
  18. Becker S, Terlau H. Toxins from cone snails: properties, applications and biotechnological production. Appl Microbiol Biotechnol. 2008;79:1-9 pubmed publisher
    ..This opens the possibility for biotechnological production of also larger amounts of long chain conopeptides for the use of these peptides in research and medical applications. ..
  19. McClellan A, Kovalenko M, Benes J, Schulz D. Spinal cord injury induces changes in electrophysiological properties and ion channel expression of reticulospinal neurons in larval lamprey. J Neurosci. 2008;28:650-9 pubmed publisher
  20. Rafalzik S, Pehl U, Ott D, Strotmann J, Wolff M, Gerstberger R. Cholinergic signal transduction in the mouse sphenopalatine ganglion. Brain Res. 2008;1241:42-55 pubmed publisher
    ..Nicotinic signal transduction did not prove to be different in GFP-positive as compared to-negative murine SPG neurons. ..
  21. Cartmell J, Kemp J, Mutel V. L-AP4 inhibition of depolarization-evoked cGMP formation in rat cerebellum. Neurosci Lett. 1997;228:191-4 pubmed
    ..The inhibitions of the 4-AP cGMP response by 10 microM L-AP4 and 30 nM omega-Agatoxin IVA were not additive, indicating that part of the actions of L-AP4 in the cerebellum involves the modulation of P-type Ca2+ channels. ..
  22. Wermeling D, Berger J. Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain. Pharmacotherapy. 2006;26:395-402 pubmed
    ..In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion. ..
  23. Snutch T. Targeting chronic and neuropathic pain: the N-type calcium channel comes of age. NeuroRx. 2005;2:662-70 pubmed
  24. Hirota K, Lambert D. Measurement of [3H]PN200-110 and [125I]omega-conotoxin MVIIA binding. Methods Mol Biol. 2006;312:147-59 pubmed
  25. Murakami M, Suzuki T, Nakagawasai O, Murakami H, Murakami S, Esashi A, et al. Distribution of various calcium channel alpha(1) subunits in murine DRG neurons and antinociceptive effect of omega-conotoxin SVIB in mice. Brain Res. 2001;903:231-6 pubmed
    ..Intrathecal injection of omega-conotoxin SVIB, an analogue of omega-conotoxin GVIA, which acts on N-type voltage-dependent calcium channels, significantly shortened the licking time in the late phase of a formalin test. ..
  26. Sato K, Raymond C, Martin Moutot N, Sasaki T, Ohtake A, Minami K, et al. Binding of Ala-scanning analogs of omega-conotoxin MVIIC to N- and P/Q-type calcium channels. FEBS Lett. 2000;469:147-50 pubmed
    ..These results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analogs. ..
  27. Morris J, Ozols D, Lewis R, Gibbins I, Jobling P. Differential involvement of N-type calcium channels in transmitter release from vasoconstrictor and vasodilator neurons. Br J Pharmacol. 2004;141:961-70 pubmed
    ..N-type channels are responsible for transmitter release from vasoconstrictor neurons innervating a muscular artery and capacitance vein, but only partly mediate release of nitric oxide and neuropeptides from pelvic vasodilator neurons. ..
  28. Kawata Y, Okada M, Murakami T, Kamata A, Zhu G, Kaneko S. Pharmacological discrimination between effects of carbamazepine on hippocampal basal, Ca(2+)- and K(+)-evoked serotonin release. Br J Pharmacol. 2001;133:557-67 pubmed
  29. Chen C, Xu R. The in vitro regulation of growth hormone secretion by orexins. Endocrine. 2003;22:57-66 pubmed
    ..It is therefore suggested that orexins may play an important role in regulating GHRH-stimulated GH secretion through an increase in the L-type Ca2+ current and the PKC-mediated signaling pathways in ovine somatotropes. ..
  30. Escames G, Macias M, Leon J, Garcia J, Khaldy H, Martin M, et al. Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum. J Neuroendocrinol. 2001;13:459-66 pubmed
    ..The results suggest that decreased Ca2+ influx is involved in the inhibitory effects of melatonin on the glutamatergic activity of rat striatum. ..
  31. Bernard C, Corzo G, Mosbah A, Nakajima T, Darbon H. Solution structure of Ptu1, a toxin from the assassin bug Peirates turpis that blocks the voltage-sensitive calcium channel N-type. Biochemistry. 2001;40:12795-800 pubmed
    ..Analysis of the electrostatic charge's repartition gives some insights about the importance of the basic residues, which could interact with acidic residues of the channel and then provide a stabilization of the toxin on the channel...
  32. Meacham C, White L, Barone S, Shafer T. Ontogeny of voltage-sensitive calcium channel alpha(1A) and alpha(1E) subunit expression and synaptic function in rat central nervous system. Brain Res Dev Brain Res. 2003;142:47-65 pubmed
    ..Overall, the results suggest that expression of voltage-sensitive Ca(2+) channels during development is dynamic and is important in central nervous system development. ..
  33. Favreau P, Gilles N, Lamthanh H, Bournaud R, Shimahara T, Bouet F, et al. A new omega-conotoxin that targets N-type voltage-sensitive calcium channels with unusual specificity. Biochemistry. 2001;40:14567-75 pubmed
    ..omega-Ctx CNVIIA thus represents a new selective tool for blocking N-type VSCC that displays a unique pharmacological profile and highlights the diversity of voltage-sensitive Ca(2+) channels in the animal kingdom. ..
  34. Silver R, Poonwasi K, Seyedi N, Wilson S, Lovenberg T, Levi R. Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Natl Acad Sci U S A. 2002;99:501-6 pubmed
  35. Goldenberg D, Koehn R, Gilbert D, Wagner G. Solution structure and backbone dynamics of an omega-conotoxin precursor. Protein Sci. 2001;10:538-50 pubmed
    ..Other studies have implicated this segment in the binding of the peptide to its physiological target, and the observed motions may play a role in allowing the peptide to enter the binding site ..
  36. Saulino M, Burton A, Danyo D, Frost S, Glanzer J, Solanki D. Intrathecal ziconotide and baclofen provide pain relief in seven patients with neuropathic pain and spasticity: case reports. Eur J Phys Rehabil Med. 2009;45:61-7 pubmed
    ..Future studies are warranted to determine the optimal dosing and titration schedules for ziconotide-baclofen usage. ..
  37. Pszczolkowski M, Olson E, Rhine C, Ramaswamy S. Role for calcium in the development of ovarial patency in Heliothis virescens. J Insect Physiol. 2008;54:358-66 pubmed
    ..The JH II, JH III and calcium-dependent component of JH I signaling pathway probably utilize calcium/calmodulin-dependent kinase II for activation of Na(+)/K(+) -ATPase. ..
  38. Wallace M. Ziconotide: a new nonopioid intrathecal analgesic for the treatment of chronic pain. Expert Rev Neurother. 2006;6:1423-8 pubmed
    ..The drug requires a slow titration in order to achieve analgesia while avoiding dose-limiting side effects. This review examines the currently available information on this new analgesic. ..
  39. Melena J, Chidlow G, Osborne N. Blockade of voltage-sensitive Na(+) channels by the 5-HT(1A) receptor agonist 8-OH-DPAT: possible significance for neuroprotection. Eur J Pharmacol. 2000;406:319-24 pubmed
    ..These data show that 8-OH-DPAT directly interacts with voltage-sensitive Na(+) channels to reduce Na(+) influx so providing an additional mechanism to explain how it functions as a neuroprotectant. ..
  40. Smith M, Cabot P, Ross F, Robertson A, Lewis R. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain. 2002;96:119-27 pubmed
  41. Freiman T, Surges R, Kukolja J, Heinemeyer J, Klar M, Van Velthoven V, et al. K(+)-evoked [(3)H]-norepinephrine release in human brain slices from epileptic and non-epileptic patients is differentially modulated by gabapentin and pinacidil. Neurosci Res. 2006;55:204-10 pubmed
  42. Druzin M, Haage D, Malinina E, Johansson S. Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals. J Physiol. 2002;542:131-46 pubmed
    ..The results are explained by a model with parallel Ca2+ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca2+-activated K+ channels at a distance from the release site. ..
  43. Meunier F, Feng Z, Molgo J, Zamponi G, Schiavo G. Glycerotoxin from Glycera convoluta stimulates neurosecretion by up-regulating N-type Ca2+ channel activity. EMBO J. 2002;21:6733-43 pubmed
    ..Therefore, glycerotoxin is a unique addition to the arsenal of tools available to unravel the mechanism controlling Ca(2+)-regulated exocytosis via the specific activation of Ca(v)2.2. ..
  44. Gandia L, Lara B, Imperial J, Villarroya M, Albillos A, Maroto R, et al. Analogies and differences between omega-conotoxins MVIIC and MVIID: binding sites and functions in bovine chromaffin cells. Pflugers Arch. 1997;435:55-64 pubmed
  45. Stix G. A toxin against pain. Sci Am. 2005;292:70-5 pubmed
  46. Cunningham S, Mihara S, Higashi H. Presynaptic calcium channels mediating synaptic transmission in submucosal neurones of the guinea-pig caecum. J Physiol. 1998;509 ( Pt 2):425-35 pubmed
  47. Martin Moutot N, de Haro L, Seagar M. [Dosage and specificity of anti-calcium channel antibodies in Lambert-Eaton myasthenic syndrome]. Rev Neurol (Paris). 2004;160:S28-34 pubmed
    ..Only 5 patients were seronegative in both tests, thus a combination of the two assays reliably detected autoantibodies in 26/31 (84%) patients. ..
  48. Jensen L, Salomonsson M, Jensen B, Holstein Rathlou N. Depolarization-induced calcium influx in rat mesenteric small arterioles is mediated exclusively via mibefradil-sensitive calcium channels. Br J Pharmacol. 2004;142:709-18 pubmed
    ..The possibility that the sustained Ca(2+) influx observed was the result of a T-type window current is discussed. ..
  49. Jablonka S, Beck M, Lechner B, Mayer C, Sendtner M. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy. J Cell Biol. 2007;179:139-49 pubmed
    ..2 accumulation and excitability. This may lead to the development of new therapies for SMA that are not focused on enhancing motoneuron survival but instead investigate restoration of growth cone excitability and function. ..
  50. Hubel K, Russ L. Mechanisms of the secretory response to luminal propionate in rat descending colon in vitro. J Auton Nerv Syst. 1993;43:219-29 pubmed
    ..We hypothesize that NaP stimulates the superficial epithelium to release an unidentified agonist that depolarizes predominantly cholinergic nerve terminals and causes colonic secretion. ..
  51. Baumrucker S. N-type calcium channel blockers: a call for papers. Am J Hosp Palliat Care. 2005;22:91-2 pubmed
  52. Sorkin L, Doom C, Maruyama K, Nanigian D. Secondary hyperalgesia in the rat first degree burn model is independent of spinal cyclooxygenase and nitric oxide synthase. Eur J Pharmacol. 2008;587:118-23 pubmed publisher
    ..Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca2+ permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre- or post-synaptically. ..
  53. Fukushima Y, Nagayama T, Kawashima H, Hikichi H, Yoshida M, Suzuki Kusaba M, et al. Role of calcium channels and adenylate cyclase in the PACAP-induced adrenal catecholamine secretion. Am J Physiol Regul Integr Comp Physiol. 2001;281:R495-501 pubmed
    ..These pathways may act independently of each other. ..