Cloning of the rat P2u receptor and its potential role in coronary vasodilation

S. Godecke, U. K. Decking, A. Godecke and J. Schrader Institut fur Herz- und Kreislaufphysiologie, Heinrich-Heine-Universitat, Dusseldorf, Germany. We cloned and sequenced the cDNA as well as the genomic DNA of the P2u receptor gene from the rat. The coding region of the gene is not interrupted by introns. P2u is expressed in a variety of rat organs with pronounced differences of expression intensities. Highest expression was found in liver and testis, while no expression could be detected in the brain. High P2u expression was found in primary microvascular endothelial cells from the rat heart, but not in cardiac myocytes. By in situ analysis, we localized P2u expression in epithelial cells of esophagus and bronchi. Functional analysis revealed that, in isolated perfused rat hearts, the P2u ligands UTP and ATP induce a pronounced vasodilation of coronary blood vessels. In contrast, UMP and uridine, the degradative products of UTP, act as potent vasoconstrictors. Our experiments suggest that, in the rat heart, endothelial P2u receptors are involved in the ATP/UTP-mediated vasodilation of coronary blood vessels.