Add time:07/31/2019         Source:sciencedirect.com

The selectivities of the diadenosine polyphosphates (ApnAs, n=2–6) at the human P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11 receptors stably expressed in 1321N1 human astrocytoma cells was determined using a Fluorescence Imaging Plate Reader (FLIPR) to measure intracellular Ca2+ mobilisation. The rank order of agonist potencies at P2Y1 were: ADP>P1,P3-diadenosine triphosphate (Ap3A)>P1,P3-diadenosine hexaphosphate (Ap6A)=P1,P3-diadenosine diphosphate (Ap2A)≫P1,P3-diadenosine pentaphosphate (Ap5A). P1,P3-diadenosine tetraphosphate (Ap4A) was inactive up to 1 mM. The rank order of agonist potencies at P2Y2 were: UTP>Ap4A≫Ap6A>Ap5A>Ap3A≫Ap2A. The Ap4A concentration response curve appeared to be bi-phasic. At P2Y4 all the ApnAs tested were inactive as agonists. At P2Y6, only Ap3A and Ap5A showed significant agonist activity. At P2Y11, only Ap4A showed significant agonist activity. ApnAs were inactive as antagonists of the P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11 receptors. At P2Y4, however, the ApnAs potentiated the UTP response.

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