ATP STIMULATES CA2+ MOBILIZATION BY A NUCLEOTIDE RECEPTOR IN GLOMERULAR ENDOTHELIAL-CELLS

The present study investigates ATP effects on Ca2+ mobilization in bovine glomerular endothelial cells (GEC) and the receptors mediating ATP response. Extracellular ATP stimulated a rise in inositol 1,4,5-trisphosphate and cytosolic free Ca2+ concentration ([Ca2+](i)) in a dose-dependent manner. Extracellular Ca2+ depletion did not prevent [Ca2+](i) rise. ATP effects were not mediated by P-1, P-2x, and P-2t purinoceptors, since the P-1 receptor agonist adenosine and the P-2x receptor agonist [alpha,beta-CH2]ATP had no effect on inositol 1-monophosphate (IP) formation and Ca2+ mobilization and ATP does not activate P-2t receptors. The P-2y receptor antagonist reactive blue (10(-3) M) had little inhibitory effect on ATP (10(-5) M)-stimulated IP formation (15.6 +/- 4.2%) and Ca2+ rise (7.0 +/- 3.0%). According to the classification of purinoceptors, ATP is less potent than 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) in stimulating P-2y receptors. In GEC, however, the rank order of potency in stimulating IP and [Ca2+](i) rise was ATP > 2-MeS-ATP > ADP. The pyrimidine nucleotide UTP (10(-3) M) induced maximal IP formation (653 +/- 37%) and Ca2+ mobilization (591 +/- 22 nM) similar to ATP (IP 647 +/- 27%; [Ca2+](i) 583 +/- 15 nM). At submaximal (10(-5) M) but not at maximal (10(-3) M) doses ATP and UTP effects were additive. ATP and UTP induced specific cross-desensitization. It is concluded that the purinergic nucleotide ATP and pyrimidine nucleotide UTP mediate their effects by a common nucleotide receptor. This receptor differs from P-2z and P-2y1 receptors, since by definition UTP does not activate these receptors. The present results demonstrate that ATP effects are mediated by a nucleotide receptor in GEC. This finding contrasts with the observation of P-2y purinoceptors mediating ATP effects in large vascular endothelial cells; however, it is similar to studies in brain capillary endothelial cells.