Insects GABA receptors

The insect GABA receptor-chloride ionophore complex is found in the CNS and also at peripheral neuromuscular sites. GABA receptors belong to a superfamily of ligand-gated ion channels known as Cys-loop receptors that include nicotinic acetylcholine receptors and glutamate-gated chloride channels (Lester, 2004). Cys-loop receptors are so named because... 

There is considerable evidence that GABA is an important neurotransmitter in the CNS of insects, although the details of insect GABA receptor pharmacology are only just beginning to emerge (4-9) ... 

The response to GABA could be potentiated by the benzodiazepine flunitrazepam (10 6M), suggesting that the insect GABA receptor may have a functional benzodiazepine site on the GABA receptor complex ... 

GABAg, insect soma) and so far there are no compounds known to be uniquely active as agonists or antagonists at the insect GABA receptor. 

Cloning the Insect GABA Receptor and Resistance Mutations... 

Rdl orthologs have since been cloned from many other insect species and, when heterologously expressed in the Xenopus oocyte expression system or in cell lines, give membrane receptors that behave like insect GABA receptors. Rdl... 

LCCH3 has 47% identity to vertebrate GABA receptor / subunits, but is unlikely to be a subunit of native insect GABA receptors. Although it can form functional heteromultimers with Rdl subunits, these are unlike any known native insect GABA receptors in that they are bicucculine-sensitive, PTX-insensitive and undergo a slow desensitization [26, 49). Furthermore, the distributions of LCCH3 and Rdl in the Drosophila nervous system do not overlap [50]. 

Dr. John E. Casida from the University of California Berkeley is inveshgating the fundamental basis for the selective toxicity of insecticides, including endosulfan, acting at the gamma-aminobutyric acid (GABA) receptor of mammals and insects. The research is sponsored by the National Institute of Environmental Health Sciences. 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remainder of this description will be restricted to this form. 

Wafford KA, Sattelle DB, Gant DB, et al. 1989. Noncompetitive inhibition of GABA receptors in insect and vertebrate CNS by endrin and lindane. Pesticide Biochem Physiol 33 213-219. 

Lummis SCR, Buckingham SD, Rauh JJ, et al. 1990. Blocking actions of heptachlor at an insect central nervous system GABA receptor. Proc R Soc Lond [Biol] 240 97-106. 

Hosie AM, Aronstein K, Sattelle DB, ffrench-Constant RH (1997) Molecular Biology of Insect Neuronal GABA Receptors. Trends Neurosci 20 578... 

Ozoe Y, Akamatsu M, Higata T, Ikeda I, Mochida K, Koike K, Ohmoto T, Nikaido T (1998) Picrodendrin and Related Terpenoid Antagonists Reveal Structural Differences Between Ionotropic GABA Receptors of Mammals and Insects. Bioorg Med Chem 6 481... 

GABA Receptors of the Insect Central Nervous System... 

Characterization of Putative Insect CNS GABA receptors by Radioligand Binding Studies... 

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