# Babraham Institute Laboratory of Molecular Signalling, Zoology Department, Cambridge University, Cambridge, UK, § Department of Biochemical Pharmacology, State University of New York, Buffalo, USA,
In insects dopamine receptor subtypes may be involved in memory and learning. Dopamine receptors belong to the G-protein coupled receptor superfamily of seven transmembrane domain proteins. Five distinct classes of dopamine receptor have been identified by cloning in mammals. These fall into two broad pharmacological categories D1-like and D2-like. A D1-like receptor affecting adenylyl cyclase activity has already been identified in Drosophila (Gotzes et al, 1994; Sugamori et al, 1995). We have recently cloned a novel G-protein coupled dopamine receptor (DopR99B), expressed in Drosophila heads, which may define a novel class of dopamine receptors (Feng et al, 1996). We report here that when expressed in Xenopus oocytes the activated DopR99B increases intracellular Ca2 levels and also increases cyclic AMP levels. The rank order of potency for biogenic amines in stimulating both second messenger effects is dopamine>norepinephrine>epinephrine>tyramine. Octopamine and 5-hydroxytryptamine are not active at concentrations up to 100uM. The pharmacological profile for synthetic antagonists on both second messenger responses was identical and suggested that DopR99B is a D1-like dopamine receptor. The pharmacological profile for synthetic agonists again suggests a D1-like dopamine receptor, but was different for the two second messenger systems assayed. Thus, DopR99B exhibits ligand-specific coupling to different second messenger systems, a phenomenon exhibited by a range of other aminergic and peptidergic G-protein coupled receptors from both invertebrates and vertebrates (Robb et al, 1994; Evans et al, 1995). This suggests that the receptor exhibits a different agonist profile for synthetic ligands depending upon which second messenger systems are assayed.