FlyBase ID : FBgn0035538
Genetic map position - chr3L:4367640-4380376
Classification - G protein-coupled chemokine receptor-like protein
Cellular location - surface transmembrane
NCBI links: Precomputed BLAST | EntrezGene Recent literature Petruccelli, E., Li, Q., Rao, Y. and Kitamoto, T. (2016). The unique dopamine/ecdysteroid receptor modulates ethanol-induced sedation in Drosophila . J Neurosci 36: 4647-4657. PubMed ID: 27098705
Steroids profoundly influence behavioral responses to alcohol by activating canonical nuclear hormone receptors and exerting allosteric effects on ion channels. Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. The dopamine/ecdysteroid receptor (DopEcR) is a GPCR that mediates nongenomic actions of ecdysteroids, the major steroid hormones in insects. This study reports that Drosophila DopEcR plays a critical role in ethanol-induced sedation. DopEcR mutants take longer than control flies to become sedated during exposure to ethanol, despite having normal ethanol absorption or metabolism. RNAi-mediated knockdown of DopEcR expression reveals that this receptor is necessary after eclosion, and is required in particular neuronal subsets, including cholinergic and peptidergic neurons, to mediate this behavior. Additionally, flies ubiquitously overexpressing DopEcR cDNA have a tendency to become sedated quickly upon ethanol exposure. These results indicate that neuronal subset-specific expression of DopEcR in adults is required for normal sedation upon exposure to ethanol. It was also found that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor /extracellular signal-regulated kinase signaling. Last, genetic and pharmacological analyses suggest that in adult flies ecdysone may serve as an inverse agonist of DopEcR and suppress the sedation-promoting activity of DopEcR in the context of ethanol exposure. These findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders.
Larvae of two polyphagous lepidopteran species, Lacanobia oleracea (Tomato moth) and Acherontia atropos (Death's head hawkmoth), have been treated with representatives of three classes of compounds which are known to interact with the ligand binding site of insect steroid hormone receptors: a steroidal ecdysteroid (20-hydroxyecdysone; 20E; agonist), two non-steroidal dibenzoylhydrazines (RH5849 and RH5992; agonists) and the triterpenoid cucurbitacin B (cucB; antagonist). Both species are unaffected by dietary 20E at concentrations up to 400 ppm. L. oleracea metabolises ingested [ 3 H ]20E to a mixture of C-22 fatty acyl esters, while A. atropos excretes [ 3 H ]20E unmetabolised. Both species are susceptible to the dibenzoylhydrazines when these are incorporated into the diet, with RH5992 proving lethal at 1 ppm and RH5849 proving lethal at 10 ppm. Thus, the metabolic/excretion mechanisms which are so effective against ingested 20E do not recognise the non-steroidal agonists. The two species showed varying degrees of tolerance to cucB; L. oleracea was unaffected by 400 ppm in the diet, while A. atropos showed effects at 400 ppm, but not at 40 ppm. Feeding cucB in conjunction with 20E or injecting cucB when the ecdysteroid titre was low or rising also had no effect in L. oleracea . It is suggested that tolerance to the two classes of natural products (ecdysteroids and cucurbitacins) is associated with the occurrence of these compounds in some of the host plants of these species; evidence is presented for the presence of phytoecdysteroids in the host plants.