Kappa-flavitoxin: isolation of a new neuronal nicotinic receptor antagonist that is structurally related to kappa-bungarotoxin

Chiappinelli, Vincent A.; Wolf, Kathleen M.; DeBin, John A.; Holt, I. Lee

doi:10.1016/0006-8993(87)91043-2

Cited by 32 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The venom of B. flaviceps is more potent than B. fasciatus but comparable in potency to B. candidus venom; the LD 50 values of B. flaviceps , B. candidus and B. fasciatus venoms are 3.5 μg, 3.2 μg and 61.7 μg per kg of experimental mouse respectively [23]. Other than the isolation and characterization of β- bungarotoxin [15,24], κ- flavitoxin [25,26] and PLA 2 [15], not much information is available on the venom of B. flaviceps . Therefore, we have here examined the venom gland of B. flaviceps by using expressed sequence tags (ESTs) to explore the venom composition in detail as well as to identify novel and low abundance toxins.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags

et al. 2010

View full text Add to dashboard Cite

BackgroundThe Red-headed krait (Bungarus flaviceps, Squamata: Serpentes: Elapidae) is a medically important venomous snake that inhabits South-East Asia. Although the venoms of most species of the snake genus Bungarus have been well characterized, a detailed compositional analysis of B. flaviceps is currently lacking.ResultsHere, we have sequenced 845 expressed sequence tags (ESTs) from the venom gland of a B. flaviceps. Of the transcripts, 74.8% were putative toxins; 20.6% were cellular; and 4.6% were unknown. The main venom protein families identified were three-finger toxins (3FTxs), Kunitz-type serine protease inhibitors (including chain B of β-bungarotoxin), phospholipase A2 (including chain A of β-bungarotoxin), natriuretic peptide (NP), CRISPs, and C-type lectin.ConclusionThe 3FTxs were found to be the major component of the venom (39%). We found eight groups of unique 3FTxs and most of them were different from the well-characterized 3FTxs. We found three groups of Kunitz-type serine protease inhibitors (SPIs); one group was comparable to the classical SPIs and the other two groups to chain B of β-bungarotoxins (with or without the extra cysteine) based on sequence identity. The latter group may be functional equivalents of dendrotoxins in Bungarus venoms. The natriuretic peptide (NP) found is the first NP for any Asian elapid, and distantly related to Australian elapid NPs. Our study identifies several unique toxins in B. flaviceps venom, which may help in understanding the evolution of venom toxins and the pathophysiological symptoms induced after envenomation.

show abstract

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Antibodies (26) and toxins that bind to the neural nicotinic AcChoR (27)(28)(29) as well as cDNA probes (30) to the neural AcChoR mRNA can be used to determine whether significant changes in the number of functional AcChoRs are involved in the dramatic induction of AcCho sensitivity after innervation described in the current study. Recent work has indicated that sympathetic neurons innervated in vitro by spinal cord explants have greater numbers of a-bungarotoxin-binding sites present on the cell surface (31,32 (8) or the increased response of sympathetic neurons to AcCho (present study), since both groups measured the current evoked by agonist applied over an =300 gum radius around the neuronal soma.…”

mentioning

confidence: 99%

Neural regulation of acetylcholine sensitivity in embryonic sympathetic neurons.

Role

1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The development of transmitter sensitivity is an important component of synaptic differentiation. Despite a wealth of information about the appearance of acetylcholine (AcCho) sensitivity at the neuromuscular junction, the onset and regulation of this critical aspect of synaptogenesis has not previously been examined for synapse formation between neurons. To determine whether there is a role of presynaptic input in the induction of AcCho sensitivity at interneuronal synapses, AcCho-induced currents were measured in embryonic sympathetic neurons before and after synapse formation in vitro. The total AcCho sensitivity of postsynaptic neurons was increased nearly 10-fold after innervation. The effects of innervation are mimicked by medium conditioned by preganglionic neurons, suggesting that presynaptic neurons regulate postsynaptic AcCho sensitivity by release of a soluble factor.These observations provide evidence that presynaptic input regulates neuronal sensitivity to an identified synaptic transmitter.Synaptogenesis between motoneurons and muscle is accompanied by both pre-and postsynaptic cell differentiation (see ref. 1 for review). A well-characterized aspect of muscle cell development with innervation is the enhanced sensitivity to transmitter at the site of nerve-muscle contact (refs. 2-4 and see refs. 5-7 for review). Arrival of the motoneuron is followed by a rapid increase in acetylcholine (AcCho) sensitivity colocalized with sites of presynaptic transmitter release (3). This is due, in part, to an increase in the number of AcCho receptors (AcChoR; see ref. 6 for review) and may depend upon a factor released from the motor nerve (see refs. 5-7 for review).In contrast to the wealth of information available on the development of AcCho sensitivity at the neuromuscular junction, this important aspect of synaptogenesis has not been studied at synapses formed between neurons. In vivo studies have been hampered by the difficulties of recording from neurons before and shortly after the arrival of presynaptic input and establishment of synapses. Although this is technically straightforward using an in vitro approach, there are few culture preparations for which synapses have been described between identified pre-and postsynaptic neurons (8-10).In the current study the developmental regulation of neuronal AcCho sensitivity with synaptogenesis was studied by using an in vitro preparation to innervate sympathetic neurons with their preganglionic partners and assay transmitter-evoked responses before and after synapse formation. This study indicates that innervation of sympathetic neurons is accompanied by a 10-fold increase in the total AcCho sensitivity. Since this enhancement of AcCho sensitivity is mimicked by medium conditioned by the preganglionic neurons, these findings suggest that neural regulation of transmitter sensitivity may play an important role in synapse formation between neurons. A preliminary account of some of these findings has been reported in abstract form (11). MATERIALS AND METHODS...

show abstract

“…Reduction and dithiopyridylation of this disulfide lowers the affinity for the α7 nAChR (Kd = 12 × 10 -6 M), but does not affect the affinity for α3-containing subtypes (Kd = 0.35 × 10 -9 M) [56]. Another κ-neurotoxin, κ-flavitoxin, also binds with high affinity to α3 subtypes of neuronal AChRs [63]; moreover, nicotinic neurotransmission in autonomic ganglia is completely blocked by 50 nM κ-flavitoxin [41].…”

Section: κ-Neurotoxinsmentioning

confidence: 96%

“…To date, four κ-neurotoxins have been identified: κ-bungarotoxin, κ-2-bungarotoxin and κ-3-bungarotoxin have been isolated from the venom of Bungarus multicinctus and κ-flavitoxin from the venom of Bungarus flaviceps [41][42][43]. The κ-neurotoxins contain 66 residues and five disulfide bonds, with the fifth disulfide bond located in the tip of loop II [44].…”

Section: κ-Neurotoxinsmentioning

confidence: 99%

Neurotoxins Acting at Nicotinic Receptors

Hogg

Bertrand

2008

Future Neurol.

View full text Add to dashboard Cite

Neurotoxins include, in the most general sense, all molecules that destroy or inhibit the proper functioning of the nervous system. Neurotoxins from animals and plants include alkaloids and peptides, many of which interact with physiological processes in a selective manner. The majority of neurotoxins disrupt the transmission of signals in the nervous system by interfering with synaptic transmission. Neurotoxins can act presynaptically to inhibit the release, uptake and recycling of neurotransmitters or postsynaptically, binding to receptors on the postsynaptic membrane and preventing their activation by neurotransmitters. A class of neurotoxins from plants and animals interact with nicotinic acetylcholine receptors, either at the neuromuscular junction, peripherally at neuronal ganglia or centrally, to produce neurotoxic effects. In this article we review current knowledge of some of these neurotoxins, their structure, pharmacology, importance as pharmaceutical tools as well as future prospects for the development of therapeutic molecules.

show abstract

Kappa-flavitoxin: isolation of a new neuronal nicotinic receptor antagonist that is structurally related to kappa-bungarotoxin

Cited by 32 publications

References 15 publications

Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags

Transcriptomic analysis of the venom gland of the red-headed krait (Bungarus flaviceps) using expressed sequence tags

Neural regulation of acetylcholine sensitivity in embryonic sympathetic neurons.

Neurotoxins Acting at Nicotinic Receptors

Contact Info

Product

Resources

About