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• W2074943318 abstract "Background and purpose: We explored the stereoselective activation of the P2Y 11 receptor, stably expressed and tagged with GFP, in 1321N1 cells, in comparison to its closest homologue, the P2Y 1 receptor. Experimental approach: The potency of several chiral ATP analogues was determined by measuring increases in intracellular calcium concentration ([Ca 2+ ] i ). In a series of ATP‐ α ‐B and ATP‐ α ‐S analogues, a non‐bridging oxygen atom of P was substituted by BH 3 or sulphur, respectively, introducing a chiral center at P. The pairs of diastereoisomers (A and B isomers) were each applied as purified compounds. Key results: The (B) isomers (ATP‐ α ‐B Sp isomers and ATP‐ α ‐S Rp isomers) of all derivatives tested were more potent at the P2Y 11 receptor than the corresponding (A) isomers (ATP‐ α ‐B Rp isomers and ATP‐ α ‐S Sp isomers) and the parent compounds. This characteristic of the P2Y 11 receptor is opposite to the behaviour of the same diastereoisomers at the P2Y 1 receptor, at which the (A) isomers are more active. Conclusions and implications: The distinctly opposite diastereoselective activity of ATP derivatives at the P2Y 11 and the P2Y 1 receptor will allow the deciphering of structural differences of the ligand recognition sites between these receptor subtypes and may aid in the development of subtype‐selective agonists. Moreover, ATP‐ α ‐B diastereoisomers are not active at the P2Y 2 receptor. Thus, they are compounds suitable for distinguishing the functional contribution of the two ATP‐activated P2Y receptors, the P2Y 2 and P2Y 11 receptor, in physiological or pathophysiological responses of cells. British Journal of Pharmacology (2006) 149 , 416–423. doi: 10.1038/sj.bjp.0706887" @default.
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• W2074943318 date "2006-10-01" @default.
• W2074943318 modified "2023-10-17" @default.
• W2074943318 title "Opposite diastereoselective activation of P2Y₁ and P2Y₁₁ nucleotide receptors by adenosine 5′-O-(<i>α</i> -boranotriphosphate) analogues" @default.
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• W2074943318 doi "https://doi.org/10.1038/sj.bjp.0706887" @default.
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