Article date: October 1994
By: José L. Boyer, Irene E. Zohn, Kenneth A. Jacobson, T. Kendall Harden, in Volume 113, Issue 2, pages 614-620
Stimulation of P2Y‐purinoceptors on turkey erythrocytes and many other cell types results in activation of phospholipase C. In contrast, we have observed recently that P2Y‐purinoceptors on C6 rat glioma cells are not coupled to phospholipase C., but rather, inhibit adenylyl cyclase.
In this study we investigated the pharmacological selectivity of the P2‐purinoceptor antagonists, suramin, reactive blue 2, and pyridoxal phosphate 6‐azophenyl 2′,4′‐disulphonic acid (PPADS) for phospholipase C‐ and adenylyl cyclase‐coupled P2Y‐purinoceptors.
In C6 glioma cells, suramin and reactive blue 2 competitively antagonized the inhibitory effect of 2MeSATP on adenylyl cyclase (pKB = 5.4 ± 0.2 and 7.6 ± 0.1, respectively), whereas PPADS at concentrations up to 100 μm had no effect.
In contrast, in the turkey erythrocyte preparation, PPADS at concentrations up to 30 μm was a competitive antagonist of P2Y‐purinoceptor‐stimulated phospholipase C activity (pKB = 5.9 ± 0.1). Suramin and reactive blue 2 produced both a shift to the right of the concentration‐effect of 2MeSATP for the activation of phospholipase C and a significant decrease in the maximal inositol phosphate response.
Turkey erythrocytes also express a phospholipase C‐coupled β‐adrenoceptor. Concentrations of PPADS that competitively inhibited the P2Y‐purinoceptor‐mediated response had only minimal effects on the activation of phospholipase C by β‐adrenoceptors. In contrast, suramin and reactive blue 2 produced a non‐competitive inhibition, characterized by decreases in the maximal response to isoprenaline with no change in the potency of this β‐adrenoceptor agonist.
The differential effect of PPADS on P2Y‐purinoceptors of C6 glioma cells and turkey erythrocytes adds further support to the idea that different P2Y‐purinoceptor subtypes mediate coupling to adenylyl cyclic and phospholipase C.
Stimulation of P2Y‐purinoceptors on turkey erythrocytes and many other cell types results in activation of phospholipase C. In contrast, we have observed recently that P2Y‐purinoceptors on C6 rat glioma cells are not coupled to phospholipase C., but rather, inhibit adenylyl cyclase.
In this study we investigated the pharmacological selectivity of the P2‐purinoceptor antagonists, suramin, reactive blue 2, and pyridoxal phosphate 6‐azophenyl 2′,4′‐disulphonic acid (PPADS) for phospholipase C‐ and adenylyl cyclase‐coupled P2Y‐purinoceptors.
In C6 glioma cells, suramin and reactive blue 2 competitively antagonized the inhibitory effect of 2MeSATP on adenylyl cyclase (pKB = 5.4 ± 0.2 and 7.6 ± 0.1, respectively), whereas PPADS at concentrations up to 100 μm had no effect.
In contrast, in the turkey erythrocyte preparation, PPADS at concentrations up to 30 μm was a competitive antagonist of P2Y‐purinoceptor‐stimulated phospholipase C activity (pKB = 5.9 ± 0.1). Suramin and reactive blue 2 produced both a shift to the right of the concentration‐effect of 2MeSATP for the activation of phospholipase C and a significant decrease in the maximal inositol phosphate response.
Turkey erythrocytes also express a phospholipase C‐coupled β‐adrenoceptor. Concentrations of PPADS that competitively inhibited the P2Y‐purinoceptor‐mediated response had only minimal effects on the activation of phospholipase C by β‐adrenoceptors. In contrast, suramin and reactive blue 2 produced a non‐competitive inhibition, characterized by decreases in the maximal response to isoprenaline with no change in the potency of this β‐adrenoceptor agonist.
The differential effect of PPADS on P2Y‐purinoceptors of C6 glioma cells and turkey erythrocytes adds further support to the idea that different P2Y‐purinoceptor subtypes mediate coupling to adenylyl cyclic and phospholipase C.
DOI: 10.1111/j.1476-5381.1994.tb17034.x
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