Cloning of the rat P-2u receptor and its potential role in coronary vasodilation

We cloned and sequenced the cDNA as well as the genomic DNA of the P-2u receptor gene from the rat. The coding region of the gene is not interrupted by introns. P-2u 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 P-2u expression was found in primary microvascular endothelial cells from the rat heart, but not in cardiac myocytes. By in situ analysis, we localized P-2u expression in epithelial cells of esophagus and bronchi. Functional analysis revealed that, in isolated perfused rat hearts, the P-2u 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 P-2u receptors are involved in the ATP/UTP-mediated vasodilation of coronary blood vessels.