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J Biol Chem
2008 Aug 29;28335:23914-21. doi: 10.1074/jbc.M800776200.
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Analgesic compound from sea anemone Heteractis crispa is the first polypeptide inhibitor of vanilloid receptor 1 (TRPV1).
Andreev YA
,
Kozlov SA
,
Koshelev SG
,
Ivanova EA
,
Monastyrnaya MM
,
Kozlovskaya EP
,
Grishin EV
.
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Venomous animals from distinct phyla such as spiders, scorpions, snakes, cone snails, or sea anemones produce small toxic proteins interacting with a variety of cell targets. Their bites often cause pain. One of the ways of pain generation is the activation of TRPV1 channels. Screening of 30 different venoms from spiders and sea anemones for modulation of TRPV1 activity revealed inhibitors in tropical sea anemone Heteractis crispa venom. Several separation steps resulted in isolation of an inhibiting compound. This is a 56-residue-long polypeptide named APHC1 that has a Bos taurus trypsin inhibitor (BPTI)/Kunitz-type fold, mostly represented by serine protease inhibitors and ion channel blockers. APHC1 acted as a partial antagonist of capsaicin-induced currents (32 +/- 9% inhibition) with half-maximal effective concentration (EC(50)) 54 +/- 4 nm. In vivo, a 0.1 mg/kg dose of APHC1 significantly prolonged tail-flick latency and reduced capsaicin-induced acute pain. Therefore, our results can make an important contribution to the research into molecular mechanisms of TRPV1 modulation and help to solve the problem of overactivity of this receptor during a number of pathological processes in the organism.
Ahern,
Polyamines are potent ligands for the capsaicin receptor TRPV1.
2006, Pubmed,
Xenbase
Ahern,
Polyamines are potent ligands for the capsaicin receptor TRPV1.
2006,
Pubmed
,
Xenbase
Anderluh,
Cytolytic peptide and protein toxins from sea anemones (Anthozoa: Actiniaria).
2002,
Pubmed
Aneiros,
A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity.
1993,
Pubmed
Antuch,
The NMR solution structure of a Kunitz-type proteinase inhibitor from the sea anemone Stichodactyla helianthus.
1993,
Pubmed
Carlton,
Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible mechanism for peripheral sensitization.
2001,
Pubmed
Castañeda,
Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus.
1995,
Pubmed
Caterina,
The capsaicin receptor: a heat-activated ion channel in the pain pathway.
1997,
Pubmed
,
Xenbase
Caterina,
Impaired nociception and pain sensation in mice lacking the capsaicin receptor.
2000,
Pubmed
Caterina,
The vanilloid receptor: a molecular gateway to the pain pathway.
2001,
Pubmed
Creighton,
Sequences of the genes and polypeptide precursors for two bovine protease inhibitors.
1987,
Pubmed
Cuypers,
Jellyfish and other cnidarian envenomations cause pain by affecting TRPV1 channels.
2006,
Pubmed
,
Xenbase
Davis,
Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.
2000,
Pubmed
Delfín,
Purification, characterization and immobilization of proteinase inhibitors from Stichodactyla helianthus.
1996,
Pubmed
Diochot,
A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.
2004,
Pubmed
,
Xenbase
Diochot,
Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4.
1998,
Pubmed
,
Xenbase
DIXON,
The determination of enzyme inhibitor constants.
1953,
Pubmed
Fritz,
[Polyvalent isoinhibitors for trypsin, chymotrypsin, plasmin and kallikreins of sea anemones (Anemonia sulcata), isolation, inhibitory behavior and amino acid composition].
1972,
Pubmed
García-Martinez,
Attenuation of thermal nociception and hyperalgesia by VR1 blockers.
2002,
Pubmed
,
Xenbase
García-Martínez,
Design and characterization of a noncompetitive antagonist of the transient receptor potential vanilloid subunit 1 channel with in vivo analgesic and anti-inflammatory activity.
2006,
Pubmed
,
Xenbase
Gasparini,
Delineation of the functional site of alpha-dendrotoxin. The functional topographies of dendrotoxins are different but share a conserved core with those of other Kv1 potassium channel-blocking toxins.
1998,
Pubmed
Grotendorst,
Purification and partial characterization of the phospholipase A2 and co-lytic factor from sea anemone (Aiptasia pallida) nematocyst venom.
1999,
Pubmed
Guo,
Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites.
1999,
Pubmed
Joubert,
Snake venoms. The amino acid sequences of two proteinase inhibitor homologues from Dendroaspis angusticeps venom.
1980,
Pubmed
Kitaguchi,
An inhibitor of TRPV1 channels isolated from funnel Web spider venom.
2005,
Pubmed
,
Xenbase
Klionsky,
A polyclonal antibody to the prepore loop of transient receptor potential vanilloid type 1 blocks channel activation.
2006,
Pubmed
Krause,
Transient receptor potential ion channels as targets for the discovery of pain therapeutics.
2005,
Pubmed
Matz,
Amplification of cDNA ends based on template-switching effect and step-out PCR.
1999,
Pubmed
Mortari,
Neurotoxins from invertebrates as anticonvulsants: from basic research to therapeutic application.
2007,
Pubmed
Norton,
Structure and structure-function relationships of sea anemone proteins that interact with the sodium channel.
1991,
Pubmed
Olivera,
Conus peptides: biodiversity-based discovery and exogenomics.
2006,
Pubmed
Perona,
Structural basis of substrate specificity in the serine proteases.
1995,
Pubmed
Planells-Cases,
Arginine-rich peptides are blockers of VR-1 channels with analgesic activity.
2000,
Pubmed
,
Xenbase
Scheidig,
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities.
1997,
Pubmed
Schweitz,
Calcicludine, a venom peptide of the Kunitz-type protease inhibitor family, is a potent blocker of high-threshold Ca2+ channels with a high affinity for L-type channels in cerebellar granule neurons.
1994,
Pubmed
Schweitz,
Kalicludines and kaliseptine. Two different classes of sea anemone toxins for voltage sensitive K+ channels.
1995,
Pubmed
,
Xenbase
Siemens,
Spider toxins activate the capsaicin receptor to produce inflammatory pain.
2006,
Pubmed
Smith,
Site-directed mutagenesis of dendrotoxin K reveals amino acids critical for its interaction with neuronal K+ channels.
1997,
Pubmed
Ständker,
A new toxin from the sea anemone Condylactis gigantea with effect on sodium channel inactivation.
2006,
Pubmed
Strydom,
Snake venom toxins. The amino acid sequence of toxin Vi2, a homologue of pancreatic trypsin inhibitor, from Dendroaspis polylepis polylepis (black mamba) venom.
1977,
Pubmed
Suput,
Cardiovascular effects of equinatoxin III from the sea anemone Actinia equina (L.).
2001,
Pubmed
Szallasi,
After a decade of intravesical vanilloid therapy: still more questions than answers.
2002,
Pubmed
Szallasi,
The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept.
2007,
Pubmed
Tang,
Antinociceptive pharmacology of N-(4-chlorobenzyl)-N'-(4-hydroxy-3-iodo-5-methoxybenzyl) thiourea, a high-affinity competitive antagonist of the transient receptor potential vanilloid 1 receptor.
2007,
Pubmed
Valtschanoff,
Vanilloid receptor VR1 is both presynaptic and postsynaptic in the superficial laminae of the rat dorsal horn.
2001,
Pubmed
Wang,
A new cytolysin from the sea anemone, Heteractis magnifica: isolation, cDNA cloning and functional expression.
2000,
Pubmed
Watters,
Tropical marine neurotoxins: venoms to drugs.
2005,
Pubmed
