Uridine nucleotide receptors and their ligands: structural, physiological, and pathophysiological aspects, with special emphasis on the nervous system.

This review presents data on metabotropic uridine nucleotide receptor subtypes (P2UR) activated by UTP, sometimes also by UDP and/or ATP. Some chemical details of receptor subtypes and ligand interactions are described. Ligand-activated P2UR subtypes may couple to different second messengers, yet little is known about the nature of the coupling G-proteins. Data evaluating UTP as a physiological ligand include UTP origin, release and metabolism and illuminate especially roles for P2UR in the nervous system. No evidence shows UTP as a synaptic transmitter; sympathetic neurons may, however, carry P2UR allowing UTP-stimulation of norepinephrine release. UTP and derivatives act as therapeutic agents in several diseases involving mutated genes of transepithelial conductance regulators, including cystic fibrosis. This focuses interest to the synthesis of new compounds. Further, therapeutically used pyrimidine and pyrimidine analogues are suspected to have CNS-pathological effects. The presently scarce information in these areas strongly underlines the need for and importance of intense research on the suspected pyrimidine derivative triggered pathology as well as on the role of P2UR receptors in physiology and pathophysiology.