Activity of diadenosine polyphosphates at P2Y receptors stably expressed in 1321N1 cells

The selectivities of the diadenosine polyphosphates (Ap(n)As, n = 2-6) at t he human P2Y(1), P2Y(2), P2Y(4), P2Y(6), and P2Y(11) receptors stably expre ssed in 1321N1 human astrocytoma cells was determined using a Fluorescence Imaging Plate Reader (FLIPR) to measure intracellular Ca2+ mobilisation. Th e rank order of agonist potencies at P2Y(1) were: ADP > P-1,P-3-diadenosine triphosphate. (AP(3)A) > P-1,P-3-diadenosine hexaphosphate (Ap(6)A) = P-1, P-3-diadenosine diphosphate (AP(2)A) much greater than P-1,P-3-diadenosine pentaphosphate (AP(5)A). P-1,P-3-diadenosine tetraphosphate (Ap(4)A) was in active up to 1 mM. The rank order of agonist potencies at P2Y(2) were: UTP > Ap(4)A much greater than Ap(6)A > Ap(5)A > Ap(3)A much greater than Ap(2) A. The Ap(4)A concentration response curve appeared to be bi-phasic. At P2Y (4) all the Ap(n)As tested were inactive as agonists. At P2Y(6), only Ap(3) A and Ap(5)A showed significant agonist activity. At P2Y(11), only Ap(4)A s howed significant agonist activity. Ap(n)As were inactive as antagonists of the P2Y(1), P2Y(2), P2Y(4), P2Y(6) and P2Y(11) receptors. At P2Y(4), howev er, the Ap(n)As potentiated the UTP response. (C) 2001 Elsevier Science B.V . All rights reserved.