Key result
PPADS acts as a noncompetitive antagonist at P2Y1 receptors but enhances P2Y2-mediated vasorelaxation to UTP in guinea pig aorta, allowing differentiation between these receptors.
PPADS can be used to differentiate between P2Y1 and P2Y2 receptors in guinea pig aorta due to its opposing effects on these receptors.
The action of the putative P2Y1-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) was studied in guinea pig aorta for potential use in the differentiation between P2Y1 and P2Y2 purine receptors. Concentration-effect curves to 2-methylthioadenosine triphosphate (2MeSATP) and uridine triphosphate (UTP), agonists at P2Y1- and P2Y2-receptor sites, respectively, and the common agonist adenosine triphosphate (ATP) were constructed in guinea pig aortic ring preparations with the tone raised by 5 microM of noradrenaline. A ranked order of agonist potency of 2MeSATP > ATP > UTP resulted from the construction of concentration response curves to vasorelaxation of the agonists. Deendothelialization virtually abolished vasorelaxation to UTP but made no significant difference to 2MeSATP-induced responses. PPADS exhibited noncompetitive inhibition at P2Y1-receptor sites by reducing the maximal response to 2MeSATP, although a trend towards a right shift of the concentration-effect curves was observed. In total contrast, PPADS enhanced P2Y2-mediated vasorelaxation to UTP by shifting the concentration-effect curves to the left and increasing maximal responses. Thus, PPADS is a noncompetitive antagonist at P2Y1 receptors but enhances responses, at least to UTP, at P2Y2 receptors in guinea pig aorta via a hitherto unknown mechanism. Thus, PPADS is a potentially useful substance that may be used for differentiation between P2Y1 and P2Y2 receptors in the guinea pig aorta.
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Payne et al. (2002) studied this question. PPADS (pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid) was evaluated on Vasorelaxation to 2MeSATP, UTP, and ATP. PPADS acts as a noncompetitive antagonist at P2Y1 receptors but enhances P2Y2-mediated vasorelaxation to UTP in guinea pig aorta, allowing differentiation between these receptors.
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