ACTIONS OF NITROMETHYLENES ON AN ALPHA-BUNGAROTOXIN-SENSITIVE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR

被引：19

作者：

BUCKINGHAM, SD

BALK, ML

LUMMIS, SCR

JEWESS, P

SATTELLE, DB

机构：

[1] UNIV CAMBRIDGE,DEPT ZOOL,BABRAHAM INST LAB MOLEC SIGNALLING,CAMBRIDGE CB2 3EJ,ENGLAND

[2] SHELL RES LTD,SITTINGBOURNE RES CTR,SITTINGBOURNE ME9 8AG,KENT,ENGLAND

来源：

NEUROPHARMACOLOGY | 1995年 / 34卷 / 06期

关键词：

PERIPLANETA AMERICANA; IDENTIFIED NEURON; INSECTICIDES; STRUCTURE-ACTIVITY;

D O I：

10.1016/0028-3908(95)00024-Z

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Nine nitromethylene analogues were tested for their actions on insect neuronal nicotinic acetylcholine receptors (nAChRs). Microelectrode recordings were used to study the actions of nitromethylenes on the cell body of an identified cockroach (Periplaneta americana) motor neurone, the fast coral depressor (D-f) in the metathoracic ganglion. Six nitromethylenes showed potent nAChR agonist actions; others were without nAChR agonist actions. Five nitromethylenes competitively displaced bound [I-125]-alpha-bungarotoxin from cockroach nervous system membranes. The rank orders of potency for the compounds determined by their depolarizing-actions and their ability to displace [I-125]-alpha-bungarotoxin binding were similar. These findings, together with toxicity data obtained on the insects, Nephotettix cinciteps and Nilaparvata lugens, support the hypothesis that insect nAChRs are molecular targets of nitromethylene insecticides. Structure-activity relationships of the nitromethylenes suggest that optimal activity at neuronal nAChRs requires the presence of an electron-withdrawing component in the region of the aryl substituent and an electron-donating component at the 3' position of the imidazolidine ring.

引用

页码：591 / 597

页数：7

共 19 条

[1]

Bai, Lummis, Leicht, Breer, Sattelle, Actions of imidacloprid and a related nitromethylene on cholinergic receptors of an identified insect motor neurone, Pesticide Science, 33, pp. 197-204, (1991)

[2]

Beers, Reich, Structure and activity of acetylcholine, Nature (Lond.), 228, pp. 917-921, (1970)

[3]

Benson, Insect nicotinic acetylcholine receptors as targets for insecticides, Progress and Prospects in insect control, (1989)

[4]

Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Analytical Biochemistry, 65, pp. 248-254, (1976)

[5]

Chiappinelli, κ-Bungarotoxin: a probe for the neuronal nicotinic receptor in the avian ciliary ganglion, Brain Res., 277, pp. 9-21, (1983)

[6]

Chiappinelli, Hue, Mony, Sattelle, κ-Bungarotoxin blocks nicotinic transmission at an identified invertebrate central synapse, J. Exp. Biol., 141, pp. 61-71, (1989)

[7]

David, Sattelle, Actions of cholinergic pharmacological agents on the cell body membrane of the fast coxal depressor motoneurone of the cockroach, Periplaneta americana, J. Exp. Biol., 108, pp. 119-136, (1984)

[8]

Leech, Jewess, Marshall, Sattelle, Nitromethylene actions on in situ and expressed insect nicotinic acetylcholine receptors, FEBS Lett., 290, pp. 90-94, (1991)

[9]

Lindstrom, Schoepfer, Whiting, Molecular studies of the neuronal nicotinic acetylcholine receptor family, Molec. Neurobiol., 1, pp. 281-337, (1987)

[10]

Liu, Casida, High affinity binding of [<sup>3</sup>H]imidacloprid to the insect acetylcholine receptor, Pestic. Biochem. Physiol., 46, pp. 40-46, (1993)

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