Rapid, Nongenomic Responses to Ecdysteroids and Catecholamines Mediated by a Novel Drosophila G-Protein-Coupled Receptor

• Published in: The Journal of neuroscience Vol. 25; no. 26; pp. 6145 - 6155
• Main Authors: Srivastava, Deepak P, Yu, Esther J, Kennedy, Karen, Chatwin, Heather, Reale, Vincenzina, Hamon, Maureen, Smith, Trevor, Evans, Peter D
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 29-06-2005; Society for Neuroscience
• Subjects: Animals; Catecholamines - physiology; Cellular/Molecular; CHO Cells; Cricetinae; DNA Primers; DNA, Complementary; Drosophila melanogaster - physiology; Drosophila Proteins - physiology; Female; Oocytes - physiology; Polymerase Chain Reaction; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Restriction Mapping; Reverse Transcriptase Polymerase Chain Reaction; Transfection; Xenopus laevis
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1005-05.2005

Nongenomic response pathways mediate many of the rapid actions of steroid hormones, but the mechanisms underlying such responses remain controversial. In some cases, cell-surface expression of classical nuclear steroid receptors has been suggested to mediate these effects, but, in a few instances, specific G-protein-coupled receptors (GPCRs) have been reported to be responsible. Here, we describe the activation of a novel, neuronally expressed Drosophila GPCR by the insect ecdysteroids ecdysone (E) and 20-hydroxyecdysone (20E). This is the first report of an identified insect GPCR interacting with steroids. The Drosophila melanogaster dopamine/ecdysteroid receptor (DmDopEcR) shows sequence homology with vertebrate beta-adrenergic receptors and is activated by dopamine (DA) to increase cAMP levels and to activate the phosphoinositide 3-kinase pathway. Conversely, E and 20E show high affinity for the receptor in binding studies and can inhibit the effects of DA, as well as coupling the receptor to a rapid activation of the mitogen-activated protein kinase pathway. The receptor may thus represent the Drosophila homolog of the vertebrate "gamma-adrenergic receptors," which are responsible for the modulation of various activities in brain, blood vessels, and pancreas. Thus, DmDopEcR can function as a cell-surface GPCR that may be responsible for some of the rapid, nongenomic actions of ecdysteroids, during both development and signaling in the mature adult nervous system.