Regulation of P2y-purinoceptor-mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration

Br J Pharmacol. 1988 Dec;95(4):1181-90. doi: 10.1111/j.1476-5381.1988.tb11754.x.

Abstract

1. ATP and ATP analogues induced prostacyclin (PGI2) secretion from human cultured umbilical vein endothelial cells. 2. The threshold active concentration for ATP was less than or equal to 1 microM. The rank order of potency of analogues was 2-chloroadenosine 5'-triphosphate (2-ClATP) greater than 2-methylthioadenosine 5'-triphosphate (2-MeSATP) greater than ATP greater than ADP, while adenosine 5'-(alpha,beta-methylene)triphosphonate, AMP and adenosine were inactive, indicating the presence of P2y-purinoceptors. 3. In contrast to their actions on P2y-receptors in guinea-pig taenia coli, isopolar analogues of 2-methylthioadenosine 5'-(beta, gamma-methylene)triphosphonate were less effective than ATP. 4. ATP and ATP analogues increased intracellular free calcium ions, [Ca2+]i, giving a rapid transient peak due predominantly to release from intracellular stores, followed by a maintained steady-state elevated level due to influx. 5. The dose-response curves for peak [Ca2+]i induced by ATP, 2-ClATP and 2-MeSATP were very similar to those for PGI2 production. 6. Elevations of [Ca2+]i, above a threshold value of 0.8-1 microM, were necessary for PGI2 production in response to P2y-receptor activation. 7. The dose relationships between PGI2 release and peak [Ca2+]i were equivalent whether [Ca2+]i was raised by ionomycin or via P2y-receptor activation by ATP or 2-ClATP, indicating that elevations of [Ca2+]i provide the major, if not the exclusive intracellular pathway for P2y-purinoceptor-mediated PGI2 synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Calcium / metabolism*
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Epoprostenol / metabolism*
  • Humans
  • Receptors, Purinergic / drug effects
  • Receptors, Purinergic / physiology*

Substances

  • Receptors, Purinergic
  • Adenosine Triphosphate
  • Epoprostenol
  • Calcium