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 the human P2Y(1), P2Y(2), P2Y(4), P2Y(6) and P2Y(11) receptors stably expressed in 1321N1 human astrocytoma cells was determined using a Fluorescence Imaging Plate Reader (FLIPR) to measure intracellular Ca(2+) mobilisation. The 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)>>P(1),P(3)-diadenosine pentaphosphate (Ap(5)A). P(1),P(3)-diadenosine tetraphosphate (Ap(4)A) was inactive up to 1 mM. The rank order of agonist potencies at P2Y(2) were: UTP>Ap(4)A>>Ap(6)A>Ap(5)A>Ap(3)A>>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 showed 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), however, the Ap(n)As potentiated the UTP response.
Patel
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K
Department of Molecular Pharmacology, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Hertfordshire, SG1 2NY, Stevenage, UK. kp16571@gsk.com
Barnes
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Camacho
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Paterson
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Boughtflower
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Cousens
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Marshall
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D000244:Adenosine Diphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D014407:Tumor Cells, Cultured; D014544:Uridine Triphosphate / Q000494:pharmacology
D015226:Dinucleoside Phosphates; C546382:P2RY1 protein, human; C109734:P2RY11 protein, human; C546385:P2RY2 protein, human; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; C012276:diadenosine pyrophosphate; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D000244:Adenosine Diphosphate; D002217:Carbachol; D002118:Calcium; D014544:Uridine Triphosphate