Single channel studies of non-competitive antagonism of a quisqualate-sensitive glutamate receptor by argiotoxin636— a fraction isolated from orb-web spider venom

Kerry, C. J.; Ramsey, R. L.; Sansom, Mark S.P.; Usherwood, P.N.R.

doi:10.1016/0006-8993(88)90647-6

Cited by 47 publications

(29 citation statements)

References 30 publications

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“…196 Polyamine-containing toxins also non-competitively antagonize quisqualate-sensitive glutamate receptors (qGluR) of invertebrates 167,[197][198][199] by closed-channel block as well as open channel block. 200,201 For example, ArgTX-636 (18) . 201 Reductions in m o were more obvious when the concentration of ArgTX-636 (18) was raised above 1 mM.…”

Section: Other Modes and Sites Of Action?mentioning

confidence: 99%

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AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular polyamines are known to modulate the function of these receptors in vivo. In this study, recent developments in the medicinal chemistry of polyamine-based ligands are given, particularly focusing on the use of solid-phase synthesis (SPS) as a tool for the facile generation of libraries of polyamine toxin analogues. Moreover, the recent development of highly potent and very selective AMPAR ligands is described. Additionally, we provide a detailed account on the mechanism and site of action of AMPAR blockade by polyamine-based ligands, including examples of how these ligands are used as tools to study AMPAR, and a comparison with their action on other ionotropic receptors.

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Section: Other Modes and Sites Of Action?mentioning

confidence: 99%

“…200,201 For example, ArgTX-636 (18) . 201 Reductions in m o were more obvious when the concentration of ArgTX-636 (18) was raised above 1 mM. However, the relationship between these invertebrate glutamate receptors and AMPAR is not clear since attempts to clone qGluR have been unsuccessful.…”

Section: Other Modes and Sites Of Action?mentioning

confidence: 99%

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Strømgaard

Mellor

2004

Medicinal Research Reviews

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“…It has to be concluded, therefore, that the flickering block is a multistep reaction (see scheme (3)), or that argiopine is supplied from an enriched phase, e.g. the liquid membrane, as discussed by Jackson & Usherwood (1988) and Kerry et al (1988a). In the present discussion we assume that a closed time of 041 ms represents the main component of the flickering block.…”

Section: Discussionmentioning

confidence: 99%

“…A single-channel study has just appeared for the locust preparation (Kerry et al 1988a). Similar to our results obtained in crayfish, very low concentrations of argiopine (< 10-9 M) blocked channels completely, the block being slowly reversible on washing.…”

Section: Discussionmentioning

confidence: 99%

“…Without application of argiopine the kinetics of glutamate-activated channels are much more complicated in locusts than in crayfish: up to four components were observed for both the open and the closed times of channels, and the kinetics have been approximated by the simple scheme (1) used for crayfish (Cull-Candy & Parker, 1982 or by a complex allosteric model (Kerry, Kits, Ramsey, Sansom & Usherwood, 1987; Kerry, Ramsey, Sansom & Usherwood, 1988b). Kerry et al (1988a) suggested that argiopine produced open channel block, but they saw some difficulties in this interpretation. In our opinion there seems to be no critical evidence against an interpretation analogous to that of the potential-dependent block in crayfish (schemes (2) and (3)).…”

Section: Discussionmentioning

confidence: 99%

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Argiopine blocks glutamate‐activated single‐channel currents on crayfish muscle by two mechanisms.

Антонов¹,

Dudél²,

Franke³

et al. 1989

The Journal of Physiology

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SUMMARY1. The effect of the spider venom argiopine on L-glutamate-activated membrane channels of crayfish muscle was investigated using the patch-clamp technique.2. When 10-2 M-glutamate and 10-9 M-argiopine were contained in the pipette solution of a cell-attached patch, bursts of openings of excitatory channels appeared after formation of the patch. These bursts ceased abruptly after variable periods of time in the range of 5 min. Higher concentrations of argiopine (up to 10-6 M) blocked more rapidly, approximately in proportion to concentration.3. The block of excitatory channels could be partially or completely reversed by hyperpolarizing the membrane by up to -190 mV from the resting potential. The time constant of the recovery of channel opening decreased with increasing hyperpolarization and was 2 ms with -160 mV hyperpolarization. Switching back from the hyperpolarized level to the resting potential, the time constant for the resulting block was about 3 s (10-7 M-argiopine). Potential-dependent block by argiopine with similar characteristics was also observed in outside-out patches.4. Up to argiopine concentrations of 10-7 M the kinetics of channel openings and of bursts measured in pre-block periods or during reversal of the block by hyperpolarization were indistinguishable from controls.5. When the potential-dependent block observed in the presence of 10-6 Margiopine and 10-2 M-glutamate was reversed by hyperpolarization, additional short closings occurred during bursts. This 'flickering block' did not change burst length appreciably, but an additional open time component (r = 0-1 ms) appeared and the average open time per burst was reduced.6. At least two reaction steps seem necessary to model the behaviour of the potential-dependent block. The flickering block may be described as intermittent blocking of the channel which does not interfere with the reactions between glutamate and the channel.

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Glutamate receptor inhibitors as potential insecticides

Eldefrawi

Anis

Eldefrawi

1993

Arch Insect Biochem Physiol

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Philanthotoxin (PhTX) is a neurotoxic constituent of the paralytic venom of the digger wasp, Philanthus triangulum. PhTX inhibits glutamate receptors of insect muscles mostly as a channel blocker, thereby producing muscle paralysis. Since glutamate receptor blockers may be of value as selective insect control agents, numerous derivatives of PhTX were synthesized and tested for their potencies as inhibitors of insect skeletal muscle glutamate receptors. Structure-activity relationship studies revealed that shortening the polyamine chain length reduced potency, and quaternarization of the nitrogen destroyed it. The potency was increased by a bulky anchoring group with moderate hydrophobicity at the end of the polyamine chain. The conversion of the tryosyl moiety to 3,5-diiodo-tyrosyl also increased potency and so did lengthening the butyryl chain from 4 to 10 carbons. Not only did PhTXs inhibit different subtypes of glutamate receptors, including the mammalian N-methyl-D-aspartate receptor, but also nicotinic receptors of insects and vertebrates. Because of this low selectively, and the hydrophilicity of the derivatives tested, which interferes with their penetration to the target receptor, these compounds cannot be used as insecticides. Nevertheless, the insect skeletal muscle glutamate receptor is a viable target for selective insecticides and major changes in PhTX structure may possibly produce derivatives that can be potential insecticides.

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Single channel studies of non-competitive antagonism of a quisqualate-sensitive glutamate receptor by argiotoxin636— a fraction isolated from orb-web spider venom

Cited by 47 publications

References 30 publications

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

AMPA receptor ligands: Synthetic and pharmacological studies of polyamines and polyamine toxins

Argiopine blocks glutamate‐activated single‐channel currents on crayfish muscle by two mechanisms.

Glutamate receptor inhibitors as potential insecticides

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