Molecular cloning and characterization of rat P2Y4 nucleotide receptor.
An intronless open reading frame encoding a protein (361aa in length) was isolated from a rat genomic library probed with a DNA fragment from rat heart. This protein showed 83% sequence identity with the human P2Y4 (hP2Y4) receptor and represents a homologue of the human pyrimidinoceptor. However, the rP2Y4 receptor is not selective for uridine nucleotides and, instead, shows an agonist potency order of ITP = ATP = ADP(pure) = UTP = ATPgammaS = 2-MeSATP = Ap4A > UDP(pure). ADP, ATPgammaS, 2-MeSATP and UDP are partial agonists. Thus, in terms of agonist profile, rP2Y4 is more like the P2U receptor subtype. The rP2Y4 receptor was reversibly antagonized by Reactive blue 2 but not by suramin which, otherwise, inhibits the hP2Y2 receptor (a known P2U receptor). Thus, rP2Y4 and the P2Y2 subtype appear to be structurally distinct forms of the P2U receptor (where ATP and UTP are equi-active) but can be distinguished as suramin-insensitive and suramin-sensitive P2U receptors, respectively.
Bogdanov
Y D
YD
Department of Anatomy and Developmental Biology, University College London.
Wildman
S S
SS
Clements
M P
MP
King
B F
BF
Burnstock
G
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D053938:DNA Fragmentation; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry; D009865:Oocytes / Q000378:metabolism; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014981:Xenopus
D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C104749:purinoceptor P2Y4; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate