Receptors responsive to extracellular uracil nucleotides

The cloning of P2Y(4) and P2Y(3) (chicken)/PZY(6) (rat, human) receptors ha s been the ultimate proof that receptors for pyrimidine nucleotides exist. However, on the basis of their structure these receptors do not constitute a family of their own but belong to the P2Y family, which thus encompasses selective purinoceptors (P2Y(1), P2Y(11)), nucleotide receptors responsive to both adenine and uracil nucleotides (P2Y(2), P2Y(8)), and pyrimidinocept ors (P2Y(4) responsive to UTP, P2Y(3)/P2Y(6) responsive to UDP). Although t he occurrence of uracil nucleotides in extracellular fluids remains poorly documented, the very existence of P2Y receptors selectively responsive to t hem strongly suggests that UTP and UDP may play a role as intercellular med iators, independently from adenine nucleotides. Northern blotting revealed an expression of the P2Y(6) receptor mRNA in human spleen, thymus, and bloo d leukocytes, as well as in Jurkat and MOLT-4 T-cell lines. Other experimen ts revealed an expression in 1 HAEo and 16HBE14o cell lines derived from th e airway epithelium. These studies suggest a possible role of the P2Y(6) re ceptor in the immune and respiratory systems. Drug Dev. Res. 45:130-134, 19 98. (C) 1998 Wiley-Liss, Inc.