敌手
竞争对手
兴奋剂
P2Y受体
受体
化学
受体拮抗剂
核苷酸
立体化学
生物化学
基因
作者
Ingrid Fricks,Savitri Maddileti,Rhonda L. Carter,Eduardo R. Lazarowski,Robert A. Nicholas,Kenneth A. Jacobson,T. Kendall Harden
标识
DOI:10.1124/jpet.108.136309
摘要
G protein-coupled P2Y receptors (P2Y-R) are activated by adenine and uracil nucleotides. The P2Y14 receptor (P2Y14-R) is activated by at least four naturally occurring UDP sugars, with UDP-glucose (UDP-Glc) being the most potent agonist. With the goal of identifying a competitive antagonist for the P2Y14-R, UDP was examined for antagonist activity in COS-7 cells transiently expressing the human P2Y14-R and a chimeric Gα protein that couples Gi-coupled receptors to stimulation of phosphoinositide hydrolysis. UDP antagonized the agonist action of UDP-Glc, and Schild analysis confirmed that the antagonism was competitive (pKB = 7.28). Uridine 5′-O-thiodiphosphate also antagonized the human P2Y14-R (hP2Y14-R) with an apparent affinity similar to that of UDP. In contrast, no antagonist activity was observed with ADP, CDP, or GDP, and other uracil analogs also failed to exhibit antagonist activity. The antagonist activity of UDP was not observed at other hP2Y-R. In contrast to its antagonist action at the hP2Y14-R, UDP was a potent agonist (EC50 = 0.35 μM) at the rat P2Y14-R. These results identify the first competitive antagonist of the P2Y14-R and demonstrate pharmacological differences between receptor orthologs.
科研通智能强力驱动
Strongly Powered by AbleSci AI