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 P1, P2x, and P2t purinoceptors, since the P1 receptor agonist adenosine and the P2x receptor agonist [alpha,beta-CH2]ATP had no effect on inositol 1-monophosphate (IP) formation and Ca2+ mobilization and ATP does not activate P2t receptors. The P2y 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 P2y 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 P2z and P2y1 receptors, since by definition UTP does not activate these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Briner
V A
VA
Department of Medicine, University Hospital, Bern, Switzerland.
Kern
F
F
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D007295:Inositol Phosphates / Q000378:metabolism; D007672:Kidney Cortex / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D007700:Kinetics; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D014544:Uridine Triphosphate / Q000494:pharmacology
D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; C049925:fura-2-am; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate