AA sequence: Gly-Gly-Lys-Pro-Asp-Leu-Arg-Pro-Cys9-His-Pro-Pro-Cys13-His-Tyr-Ile-Pro-Arg-Pro-Lys-Pro-Arg-OH
Disulfide bonds: Cys9-Cys13
Length (aa): 22
Formula: C112H175N37O26S2
Molecular Weight: 2520 Da
Appearance: White lyophilized solid
Solubility: water or saline buffer
CAS number: NA
Source: Synthetic
Waglerin-1
Waglerin-1 blocks muscle-type nAChRs
Waglerin-1 (Wtx-1) is a peptide originally isolated from the venom of the Wagler’s pit viper (Trimeresurus wagleri). This 22 amino-acid peptide is a competitive antagonist of muscle nicotinic acetylcholine receptors. Waglerin-1 competes with α-bungarotoxin.
Waglerin-1 is an interesting tool to discriminate between fetal and adult muscle nAChRs as it binds to the α-ε subunit interface with a ~ 2000 fold higher affinity than to the α-γ or α-δ subunits. Waglerin-1 is known to bind 100 fold more potently to nAChR from adult mice than that from rat or humans. It blocks muscle nAChR from adult mice with an IC50 value of 50nM.
Some studies have demonstrated that Waglerin-1 has an effect on ionotropic GABA receptors. It may potentiate or depress I(GABA) depending on the neurons.
Some derivatives of Waglerin-1 are currently used in cosmetics to reduce wrinkles.
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Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor
Although the neuromuscular nicotinic acetylcholine receptor (nAChR) is one of the most intensively studied ion channels in the nervous system, the differential roles of fetal and adult subtypes of the nAChR under normal and pathological conditions are still incompletely defined. Until recently, no pharmacological tools distinguished between fetal and adult subtypes. Waglerin toxins (from snake venom) & alphaA(S)-conotoxins (from cone-snail venom) have provided such tools. Because these peptides were characterized by different research groups using different methods, we have: 1) more extensively tested their subtype selectivity, and 2) begun to explore how these peptides may be used in concert to elucidate expression patterns and functions of fetal and adult nAChRs. In heterologous expression systems and native tissues, Waglerin-1 & an alphaA(S)-conotoxin analog, alphaA-OIVA[K15N], are high-affinity, highly selective inhibitors of the adult and fetal muscle nAChRs, respectively. We have used the peptides and their fluorescent derivatives to explore the expression and function of the fetal and adult nAChR subtypes. While fluorescent derivatives of these peptides indicated a gradual transition from fetal to adult muscle nAChRs in mice during the first 2 weeks postnatal, we unexpectedly observed a steeper transition in functional expression in the mouse diaphragm muscle using electrophysiology. As a toolkit of pharmacological agents with complementary specificity, alphaA-OIVA[K15N] & Waglerin-1 should have further utility in determining the roles of fetal & adult nAChR subtypes in development, in mature tissues, and under pathological conditions.
Teichert RW. et al. Peptide-toxin tools for probing the expression and function of fetal and adult subtypes of the nicotinic acetylcholine receptor. Ann N Y Acad Sci. PMID: 18567854
Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor
Sellin LC. et al. Conformational analysis of a toxic peptide from Trimeresurus wagleri which blocks the nicotinic acetylcholine receptor. Biophys J. 1996. PMID: 8770182
Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors
Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor
McArdle JJ. et al. Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor. J Pharmacol Exp Ther. PMID: 10087048
Waglerin-1 inhibits GABA(A) current of neurons in the nucleus accumbens of neonatal rats. Brain Res
The effect of Waglerin-1, a 22-amino acid peptide purified from the venom of Wagler’s pit viper on the whole cell current response (I(GABA)) to gamma-aminobutyric acid (GABA) was examined for neurons freshly isolated from the nucleus accumbens of 3- to 7-day-old rats. Waglerin-1 depressed I(GABA) induced by subsaturating concentrations of GABA; the IC(50) for I(GABA) induced by 10 microM GABA was 2.5 microM Waglerin-1. This concentration of Waglerin-1 shifted the GABA concentration-response curve to the right in a parallel manner, increasing the GABA EC(50) from 12+/-3 to 27+/-5 microM. The depressant effect of Waglerin-1 was greater at negative holding potentials. Zn(2+) also inhibited I(GABA) with an IC(50) of 0.3 microM. Phosphorylation state appeared to modulate GABA(A) receptor sensitivity to the inhibitory effect of Waglerin-1 since dialysis of neurons with N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl (H-89), an inhibitor of protein kinase A, prevented inhibition. The data are discussed in terms of developmental influences on the subunit composition of GABA(A) receptors in neurons of the nucleus accumbens.
Ye JH. et al. Waglerin-1 inhibits GABA(A) current of neurons in the nucleus accumbens of neonatal rats. Brain Res. 1999. PMID: 10433985