Identification of zebrafish A2 adenosine receptors and expression in developing embryos.
The A2A adenosine receptor (AdR) subtype has emerged as an attractive target in the pursuit of improved therapy for Parkinson's disease (PD). This report focuses on characterization of zebrafish a2 AdRs. By mining the zebrafish EST and genomic sequence databases, we identified two zebrafish a2a (adora2a.1 and adora2a.2) genes and one a2b (adora2b) AdR gene. Sequence comparisons indicate that the predicted zebrafish A2 AdR polypeptides share 62-74% amino acid identity to mammalian A2 AdRs. We mapped the adora2a.1 gene to chromosome 8, the adora2a.2 gene to chromosome 21, and the adora2b gene to chromosome 5. Whole mount in situ hybridization analysis indicates zebrafish a2 AdR genes are expressed primarily within the central nervous system (CNS). Zebrafish are known to be sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that causes selective loss of dopaminergic neurons and PD-like symptoms in humans as well as in animal models. Here we show that caffeine, an A2A AdR antagonist, is neuroprotective against the adverse effects of MPTP in zebrafish embryos. These results suggest that zebrafish AdRs may serve as useful targets for testing novel therapeutic strategies for the treatment of PD.
Boehmler
Wendy
W
Department of Pharmacology, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Petko
Jessica
J
Woll
Matthew
M
Frey
Colleen
C
Thisse
Bernard
B
Thisse
Christine
C
Canfield
Victor A
VA
Levenson
Robert
R
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D002110:Caffeine / Q000494:pharmacology; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002874:Chromosome Mapping; D004247:DNA; D020869:Gene Expression Profiling; D006801:Humans; D007814:Larva / Q000187:drug effects; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000009:adverse effects; D010300:Parkinson Disease / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis / Q000235:genetics; D043704:Receptor, Adenosine A2B / Q000096:biosynthesis / Q000235:genetics; D043683:Receptors, Adenosine A2 / Q000096:biosynthesis* / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D019170:Somites / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*
D058917:Adenosine A2 Receptor Antagonists; D000697:Central Nervous System Stimulants; D009498:Neurotoxins; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043683:Receptors, Adenosine A2; D029961:Zebrafish Proteins; C540285:adora2aa protein, zebrafish; C540286:adora2ab protein, zebrafish; C540287:adora2b protein, zebrafish; D002110:Caffeine; D004247:DNA; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine