Peptide Toxins from Marine Snails with Activity on Potassium Channels and/or Currents.

Toxins from snails are peptides characterized by a great structural and functional diversity. They have a high affinity for a wide range of membrane proteins such as ion channels, neurotransmitter transporters, and G protein-coupled receptors. Potassium ion channels are integral proteins of cell membranes that play vital roles in physiological processes in muscle and neuron cells, among others, and reports in the literature indicate that perturbation in their function (by mutations or ectopic expression) may result in the development and progression of different ailments in humans.

κO-SrVIA Conopeptide, a Novel Inhibitor Peptide for Two Members of the Human EAG Potassium Channel Family.

The first conotoxin affecting the voltage-gated potassium channels of the EAG family was identified and characterized from the venom of the vermivorous species from the Gulf of Mexico. This conopeptide, initially named Cs68 and later designated κO-SrVIA, is extremely hydrophobic and comprises 31 amino acid residues, including six Cysteines in the framework VI/VII, and a free C-terminus. It inhibits the currents mediated by two human EAG subtypes, Kv10.

A subfraction obtained from the venom of the tarantula contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels.

Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds.

The T-1 conotoxin μ-SrVA from the worm hunting marine snail Conus spurius preferentially blocks the human Na1.5 channel.

Conotoxin sr5a had previously been identified in the vermivorous cone snail Conus spurius. This conotoxin is a highly hydrophobic peptide, with the sequence IINWCCLIFYQCC, which has a cysteine pattern "CC-CC" belonging to the T-1 superfamily. It is well known that this superfamily binds to molecular targets such as calcium channels, G protein-coupled receptors (GPCR), and neuronal nicotinic acetylcholine receptors (nAChR) and exerts an effect mainly in the central nervous system.

A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail , of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors.

We isolated a new dimeric conotoxin with inhibitory activity against neuronal nicotinic acetylcholine receptors. Edman degradation and transcriptomic studies indicate a homodimeric conotoxin composed by two chains of 47 amino acid in length. It has the cysteine framework XX and 10 disulfide bonds.

Sea anemone Bartholomea annulata venom inhibits voltage-gated Na channels and activates GABA receptors from mammals.

Toxin production in nematocysts by Cnidaria phylum represents an important source of bioactive compounds. Using electrophysiology and, heterologous expression of mammalian ion channels in the Xenopus oocyte membrane, we identified two main effects produced by the sea anemone Bartholomea annulata venom. Nematocysts isolation and controlled discharge of their content, revealed that venom had potent effects on both voltage-dependent Na (Na) channels and GABA type A channel receptors (GABAR), two essential proteins in central nervous system signaling.

A short framework-III (mini-M-2) conotoxin from the venom of a vermivorous species, Conus archon, inhibits human neuronal nicotinic acetylcholine receptors.

The venoms of Conus snails contain neuroactive peptides named conotoxins (CTXs). Some CTXs are nicotinic acetylcholine receptor (nAChRs) antagonists. nAChRs modulate the release of neurotransmitters and are implicated in several pathophysiologies.

Identification of Novel Conotoxin Precursors from the Cone Snail by High-Throughput RNA Sequencing.

Marine gastropods of the genus , comprising more than 800 species, have the characteristic of injecting worms and other prey with venom. These conopeptide toxins, highly diverse in structure and action, are highly potent and specific for their molecular targets (ion channels, receptors, and transporters of the prey's nervous system), and thus are important research tools and source for drug discovery. Next-generation sequencing technologies are speeding up the discovery of novel conopeptides in many of these species, but only limited information is available for , which inhabits sandy mud.

Thrombin Cleaves Prolactin Into a Potent 5.6-kDa Vasoinhibin: Implication for Tissue Repair.

Vasoinhibin is an endogenous prolactin (PRL) fragment with profibrinolytic, antivasopermeability, and antiangiogenic effects. The fact that blood clotting, vascular permeability, and angiogenesis are functionally linked during the wound-healing process led us to investigate whether thrombin, a major protease in tissue repair, generates vasoinhibin. Here, we have incubated human PRL with thrombin and analyzed the resulting proteolytic products by Western blot, mass spectrometry, high-performance liquid chromatography purification, recombinant production, and bioactivity.

Studies of Conorfamide-Sr3 on Human Voltage-Gated Kv1 Potassium Channel Subtypes.

Recently, Conorfamide-Sr3 (CNF-Sr3) was isolated from the venom of and was demonstrated to have an inhibitory concentration-dependent effect on the K channel. The voltage-gated potassium channels play critical functions on cellular signaling, from the regeneration of action potentials in neurons to the regulation of insulin secretion in pancreatic cells, among others. In mammals, there are at least 40 genes encoding voltage-gated K channels and the process of expression of some of them may include alternative splicing.

Effect of pterois volitans (lionfish) venom on cholinergic and dopaminergic systems.

Pterois volitans venom induces muscular fibrillation, which results from nerve transmission caused by the presence of acetylcholine (ACh). It also has cardiovascular effects that are due to its actions on muscarinic and nicotinic cholinergic receptors. In this study, we characterized the effects of P.

Rat aorta relaxation induced by the venom of Poecilotheria regalis involves the activation of the NO/cGMP pathway.

Spider venoms are widely recognized as a new emerging source of potential research tools, pesticides, drug leads, and therapeutic agents. Some studies suggest that these venoms may contain interesting vasodilator compounds with potential therapeutic applications. In the present study, the vasodilator activity of the venom of Poecilotheria regalis was evaluated in isolated rat aortic rings.

Cloning and expression of the recombinant crustacean hyperglycemic hormone isoform B2 (rCHH-B2) and its effects on the metabolism and osmoregulation of the Pacific white shrimp Litopenaeus vannamei.

Crustacean hyperglycemic hormones (CHHs) are multifunctional neuropeptides ubiquitous in crustaceans. In Litopenaeus vannamei, CHH-B2 is a CHH eyestalk isoform whose expression has been shown to vary with enviromental conditions, suggesting its relevance for ecophysiological performance of shrimp, controlling processes related to metabolism and osmo-ionic regulation. To study the involvement of CHH-B2 in these processes, we cloned and expressed a recombinant version with a free C-terminal glycine (rCHH-B2-Gly) in the methylotrophic yeast Pichia pastoris.

Conorfamide-Sr3, a structurally novel specific inhibitor of the Shaker K channel.

Conorfamides (CNFs) are toxins initially characterized from the venom duct of the venomous marine snail Conus spurius from the Gulf of Mexico; at their C-termini, these toxins are amidated and have high sequence similarity with the molluskan cardioexcitatory tetrapeptide Phe-Met-Arg-Phe-NH (FMRFamide or FMRFa) and other FMRFa-related peptides (FaRPs) found in the five molluskan classes, and in other invertebrate and vertebrate phyla. These peptides were the first FaRPs found to be present in any venom, and they are biologically active in mice, limpets, and/or freshwater snails. However, the molecular targets of the known CNFs (CNF-Sr1 and CNF-Sr2 from C.

A Comprehensive Proteomic Study of the Skin Secretions of the Frog Lithobates spectabilis.

Disulfide C-terminal loop fragments derived from AMPs and the presence of peptidases have been previously reported in the skin secretions of different amphibians. However, there are only a few studies on the identification of enzymes in frog skin secretion based on the primary structure of these proteins. Similarly, little data exist regarding the identification of disulfide C-terminal loops at large scale.

A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target.

A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation.

Glycine-rich conotoxins from the Virgiconus clade.

Cone snails in the Virgiconus clade prey on marine worms. Here, we identify six related conotoxins in the O1-superfamily from three species in this clade, Conus virgo, Conus terebra and Conus kintoki. One of these peptides, vi6a, was directly purified from the venom of C.

Hyperglycemic activity of the recombinant crustacean hyperglycemic hormone B1 isoform (CHH-B1) of the Pacific white shrimp Litopenaeus vannamei.

Crustacean hyperglycemic hormone (CHH) is the most abundant neuropeptide produced by the X-organ/sinus gland (XO/SG) complex in the crustacean eyestalk. CHH plays a principal role in the control of glucose metabolism. The CHH-B1 isoform is produced in the eyestalk of Litopenaeus vannamei by alternative splicing of the chhB gene and its cDNA sequence has revealed that this isoform has a non-amidated C-terminal residue (CHH-like peptide).

Preliminary results of the in vivo and in vitro characterization of a tentacle venom fraction from the jellyfish Aurelia aurita.

The neurotoxic effects produced by a tentacle venom extract and a fraction were analyzed and correlated by in vivo and in vitro approaches. The tentacle venom extract exhibited a wide range of protein components (from 24 to >225 kDa) and produced tetanic reactions, flaccid paralysis, and death when injected into crabs. Two chromatography fractions also produced uncontrolled appendix movements and leg stretching.

Arrhythmogenic effect of a crude extract from sea anemone Condylactis gigantea: possible involvement of rErg1 channels.

Sea anemones possess a number of peptide toxins that target ion channels which provide powerful tools to study the molecular basis of diverse signaling pathways. It is also acknowledged that currents through Erg1 K(+) channels in cardiac myocytes are important for electrical stability of the heart and alterations in its activity has been linked to the onset of a potentially life-threatening heart condition named long QT syndrome type 2. Here, we report that a crude extract from sea anemone Condylactis gigantea significantly increases the QT interval and has arrhythmogenic effects in the rat heart.

A novel arrangement of Cys residues in a paralytic peptide of Conus cancellatus (jr. syn.: Conus austini), a worm-hunting snail from the Gulf of Mexico.

The present study details the purification, the amino acid sequence determination, and a preliminary characterization of the biological effects in mice of a new conotoxin from the venom of Conus cancellatus (jr. syn.: Conus austini), a worm-hunting cone snail collected in the western Gulf of Mexico (Mexico).

Precursor De13.1 from Conus delessertii defines the novel G gene superfamily.

Peptide de13a was previously purified from the venom of the worm-hunting cone snail Conus delessertii from the Yucatán Channel, México. This peptide has eight cysteine (Cys) residues in the unique arrangement C-C-C-CC-C-C-C, which defines the cysteine framework XIII ("-" represents one or more non-Cys residues). Remarkably, δ-hydroxy-lysine residues have been found only in conotoxin de13a, which also contains an unusually high proportion of hydroxylated amino acid residues.