The sulfoximines, as exemplified by sulfoxaflor ([N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ(4)-sulfanylidene] cyanamide] represent a new class of insecticides. Sulfoxaflor exhibits a high degree of efficacy against a wide range of sap-feeding insects, including those resistant to neonicotinoids and other insecticides. Sulfoxaflor is an agonist at insect nicotinic acetylcholine receptors (nAChRs) and functions in a manner distinct from other insecticides acting at nAChRs. The sulfoximines also exhibit structure activity relationships (SAR) that are different from other nAChR agonists such as the neonicotinoids. This review summarizes the sulfoximine SAR, mode of action and the biochemistry underlying the observed efficacy on resistant insect pests, with a particular focus on sulfoxaflor.

No abstract

The Drosophila trp gene encodes a light-activated Ca(2+) channel subunit, which is a prototypical member of a novel class of channel proteins. Previously identified trp mutants are all recessive, loss-of-function mutants characterized by a transient receptor potential and the total or near-total loss of functional TRP protein. Although retinal degeneration does occur in these mutants, it is relatively mild and slow in onset. We report herein a new mutant, Trp(P365), that does not display the transient receptor potential phenotype and is characterized by a substantial level of the TRP protein and rapid, semi-dominant degeneration of photoreceptors. We show that, in spite of its unusual phenotypes, Trp(P365) is a trp allele because a Trp(P365) transgene induces the mutant phenotype in a wild-type background, and a wild-type trp transgene in a Trp(P365) background suppresses the mutant phenotype. Moreover, amino acid alterations that could cause the Trp(P365) phenotype are found in the transmembrane segment region of the mutant channel protein. Whole-cell recordings clarified the mechanism underlying the retinal degeneration by showing that the TRP channels of Trp(P365) are constitutively active. Although several genes, when mutated, have been shown to cause retinal degeneration in Drosophila, the underlying mechanism has not been identified for any of them. The present studies provide evidence for a specific mechanism for massive degeneration of photoreceptors in Drosophila. Insofar as some human homologs of TRP are highly expressed in the brain, a similar mechanism could be a major contributor to degenerative disorders of the brain.

The trp and trpl genes are thought to encode two classes of light-activated ion channels in Drosophila. A previous report indicated that a null trpl mutant does not display any mutant phenotype. This lack of detectable mutant phenotypes made it difficult to suggest functions for the transient receptor potentiallike (TRPL) channel in photoreceptor responses. Here, the properties of trpl photoreceptor responses were studied by using electroretinogram (ERG) and intracellular recording techniques in combination with light stimuli of relatively long durations. Distinct mutant phenotypes were detectable under these conditions. These consisted of a reduced sustained component, oscillations superimposed on the response, a poststimulus hyperpolarization, and altered adaptation properties to dim background light. Comparison of photoreceptor responses obtained from wild type, trp, and trpl showed that the responses obtained from the trp and trpl null mutants did not sum up to that of the wild-type response. To explain the nonlinear summation at the peak of the response, Reuss et al. (1997) proposed that Ca 2ϩ ions entering through the TRP channel modulate TRP and TRPL channel activities differentially. However, nonlinear summation was present not only at the peak but throughout the duration of response. Two lines of evidence are presented to suggest that, in addition to the interaction proposed by Reuss et al. (1997), there are other forms of interactions between TRP and TRPL channels, probably involving the channel proteins themselves. Key words: Drosophila; phototransduction; trpl phenotypes; TRP channel; TRPL channel; channel interactionsDrosophila photoreceptors respond to light with a depolarization mediated by a phospholipase C (PLC)-dependent signaling pathway (Bloomquist et al., 1988), resulting in the opening of two types of cation channels, transient receptor potential (TRP) and TRPlike (TRPL). The mechanism of activation of either channel is not known. The TRP and TRPL channel subunits are encoded by the transient receptor potential (trp) and trp-like (trpl ) genes, respectively (Montell and Rubin, 1989;Wong et al., 1989;Phillips et al., 1992). The protein products of trp and trpl share 39% amino acid identity and some homology to neuronal voltage-gated channel subunits, although neither TRP nor TRPL is voltage-gated (Stüh-mer et al., 1989;Phillips et al., 1992). The TRP channel is highly calcium-permeable, whereas the TRPL channel is nonspecifically cation-selective (Hardie and Minke, 1992;Niemeyer et al., 1996;Reuss et al., 1997).Previous workers have demonstrated that trp mutants exhibit severely impaired photoreceptor responses (Cosens and Manning, 1969;Minke et al., 1975;Pak, 1979;Minke, 1982). However, a null trpl mutant, trpl 302 , has been reported not to show any mutant phenotype (Niemeyer et al., 1996), raising questions about the role of the TRPL channel in phototransduction. It was suggested that TRP and TRPL might play overlapping roles. Subsequently, Reuss et al. (1997) showed differences in ionic ...

No abstract