title: Characterization of the Drosophila adenosine receptor: the effect of adenosine analogs on cAMP signaling in Drosophila cells and their utility for in vivo experiments.
abstract: Adenosine receptors (AR) belonging to the G protein-coupled receptor family influence a wide range of physiological processes. Recent elucidation of the structure of human A2AR revealed the conserved amino acids necessary for contact with the Ado moiety. However, the selectivity of Ado analogs for AR subtypes is still not well understood. We have shown previously that the Drosophila adenosine receptor (DmAdoR) evokes an increase in cAMP and calcium concentration in heterologous cells. In this study, we have characterized the second-messenger stimulation by endogenous DmAdoR in a Drosophila neuroblast cell line and examined a number of Ado analogs for their ability to interact with DmAdoR. We show that Ado can stimulate cAMP but not calcium levels in Drosophila cells. We found one full and four partial DmAdoR agonists, as well as four antagonists. The employment of the full agonist, 2-chloroadenosine, in flies mimicked in vivo the phenotype of DmAdoR over-expression, whereas the antagonist, SCH58261, rescued the flies from the lethality caused by DmAdoR over-expression. Differences in pharmacological effect of the tested analogs between DmAdoR and human A2AR can be partially explained by the dissimilarity of specific key amino acid residues disclosed by the alignment of these receptors.
authors.affiliation: Biology Centre Czech Acad. Sci. and Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Kucerova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Broz
authors.forename: Jana
authors.initials: J
authors.lastname: Fleischmannova
authors.forename: Eva
authors.initials: E
authors.lastname: Santruckova
authors.forename: Roman
authors.initials: R
authors.lastname: Sidorov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dolezal
authors.forename: Michal
authors.initials: M
authors.lastname: Zurovec
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011743:Pyrimidines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013534:Survival; D014230:Triazoles / Q000494:pharmacology
chemical_list: C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D000596:Amino Acids; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014230:Triazoles; D015762:2-Chloroadenosine; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium