Endogenous extracellular purine nucleotides redirect alpha2-adrenoceptor signaling

Abstract

Many receptors coupled to inhibitory Go/Gi-type G proteins often also produce stimulatory signals like Ca2+ mobilisation. When expressed in CHO cells the alpha2-adrenoceptor subtypes alpha2A, alpha2B and alpkha2C mobilised Ca2+. These responses were strongly reduced by the P2Y-purinoceptor antagonist suramin. A large proportion of the total pool of purine nucleotides was found extracellularly. Removal of extracellular nucleotides with apyrase or by constant perfusion had a similar effect as suramin. These treatments did not affect the alpha2-adrenoceptor-mediated inhibition of cAMP production. This indicates that cells may be primed or their signaling pathways redirected towards Ca2+ mobilisation by 'autocrine' release of nucleotides.