Evidence that rat hepatocytes co-express functional P2Y(1) and P2Y(2) receptors

1 Previous studies have indicated the expression of multiple P2Y receptors by rat hepatocytes although they have nor been identified. Here we show by reverse transcriptase-polymerase chain reaction (RT-PCR) that rat hepatocyt es express mRNA encoding all of the four cloned rat P2Y receptors (P2Y(1), P2Y(2), P2Y(4) and P2Y(6)). 2 The effects of UTP have been examined on single aequorin-injected rat hep atocytes. The [Ca2+](i) transients induced by UTP were indistinguishable fr om those induced by ATP in the same cell. The modulatory effects of elevate d intracellular cyclic AMP concentration were the same on both UTP- and ATP -induced [Ca2+](i) transients. 3 UDP, an agonist at the P2Y(6) receptor, filled to induce transients in he patocytes, indicating that functional P2Y(6) receptors coupled to increased [Ca2+](i) are not expressed. 4 The transients evoked by ADP were more sensitive to inhibition by suramin than those induced by either ATP or UTP. Within an individual cell, the tr ansients induced by ATP and UTP were inhibited by the same concentration of suramin. This sensitivity of ATP and UTP responses to suramin suggests act ion through P2Y(2) rather than P2Y(4) receptors. 5 Co-application of 30 mu M pyridoxalphosphate-6-azophenyl-2',4'-disulphoni c acid (PPADS) caused a decrease in frequency and amplitude of transients i nduced by ADP. ATP- and UTP-induced transients also displayed a decrease in amplitude in response to addition of PPADS, but this was accompanied by an increase in frequency of transients. 6 In conclusion the data presented here are consistent with the co-expressi on of P2Y(1) and P2Y(2) receptors by rat hepatocytes.