Abstract
Effects of reactive red 2 and its parent compound acid red 33 were studied in rat vas deferens and guinea-pig taenia coli. In rat vas deferens, reactive red 2 (1 to 10 μM) shifted the concentration-response curve for the PZx-purinoceptor-mediated contraction effect of α, \-methylene ATP slightly to the right and progressively decreased the maximum (apparent antagonist Kd value 0.42 μM). Acid red 33 (1000 μM) shifted the curve to the right without changing the maximum (apparent Kd 386 μM). The concentration-contraction curve of noradrenaline was not altered by reactive red 2. In the carbachol-precontracted guinea-pig taenia coli, reactive red 2 (0.1 to 10 μM) shifted the concentration-response curve for the P2Y-purinoceptor-mediated relaxation effect of adenosine 5′-O-(2-thiodiphosphate) (ADP&S) progressively to the right; only at the highest concentration of antagonist (10 μM) was the maximum slightly depressed; a pA2 value of 7.55 (Kd 0.028 μM) was derived from the shift. Acid red 33 (1000 μM) shifted the concentration-relaxation curve of ADP\S to the right without changing the maximum (apparent Kd 171 μM). Reactive red 2 (1 to 10 μLM) also shifted the concentration-response curve for the relaxation effect of α, \-methylene ATP, which is mediated by an unclassified P2-purinoceptor, progressively to the right but simultaneously decreased the maximum (apparent Kd1.6 μM). The concentration-relaxation curve of 2-chloroadenosine was not altered by reactive red 2. Pieces of vas deferens and taenia coli degraded 76 and 66 % of added ATP (10 μM) within 30 min, respectively. Reactive red 2 (0.1 to 100 μM) progressively reduced this degradation by up to 95%, with IC50values of 3.9 ± 0.6 and 3.9 ± 2.3 μM, respectively. Acid red 33 (1000 μM) reduced the degradation by 30 and 20%, respectively.
The results indicate that reactive red 2 is a relatively potent antagonist at both PZx-purinoceptors in rat vas deferens and P2Y-purinoceptors in guinea-pig taenia coli, with a 15 fold selectivity for the P2Y-purinoceptor. It inhibits ecto-nucleotidase in both tissues. The dichloro-triazine residue that distinguishes the compound from acid red 33 greatly enhances the potency at both receptor subtypes as well as at the nucleotidase. As regards P2-purinoceptor subtypes, the results confirm the existence of two relaxation-mediating P2-purinoceptors in guinea-pig taenia coli.
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Bültmann, R., Starke, K. Reactive red 2: a P2y-selective purinoceptor antagonist and an inhibitor of ecto-nucleotidase. Naunyn-Schmiedeberg's Arch Pharmacol 352, 477–482 (1995). https://doi.org/10.1007/BF00169380
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DOI: https://doi.org/10.1007/BF00169380