Premium
Regulation of P 2y ‐purinoceptor‐mediated prostacyclin release from human endothelial cells by cytoplasmic calcium concentration
Author(s) -
Carter Thomas D.,
Hallam Trevor J.,
Cusack Noel J.,
Pearson Jeremy D.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11754.x
Subject(s) - ionomycin , adenosine , purinergic receptor , prostacyclin , intracellular , adenosine triphosphate , biology , medicine , calcium , calcium in biology , endocrinology , biophysics , receptor , biochemistry
1 ATP and ATP analogues induced prostacyclin (PGI 2 ) secretion from human cultured umbilical vein endothelial cells. 2 The threshold active concentration for ATP was ≤ 1 μ m . The rank order of potency of analogues was 2‐chloroadenosine 5′‐triphosphate (2‐C1ATP) > 2‐methylthioadenosine 5′‐triphospate (2‐MeSATP) > ATP > ADP, while adenosine 5′‐(α,βfanethylene)triphosphonate, AMP and adenosine were inactive, indicating the presence of P 2y ‐purinoceptors. 3 In contrast to their actions on P 2y ‐receptors in guinea‐pig taenia coli, isopolar analogues of 2‐methylthioadenosine 5′‐(β,γ‐methylene)triphosphonate were less effective than ATP. 4 ATP and ATP analogues increased intracellular free calcium ions, [Ca 2+ ] 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 [Ca 2+ ] i induced by ATP, 2‐C1ATP and 2‐MeSATP were very similar to those for PGI 2 production. 6 Elevations of [Ca 2+ ] i , above a threshold value of 0.8–1 μ m , were necessary for PGI 2 production in response to P 2y ‐receptor activation. 7 The dose relationships between PGI 2 release and peak [Ca 2+ ] i were equivalent whether [Ca 2+ ] i was raised by ionomycin or via P 2y ‐receptor activation by ATP or 2‐ClATP, indicating that elevations of [Ca 2+ ] i provide the major, if not the exclusive intracellular pathway for P 2y ‐purinoceptor‐mediated PGI 2 synthesis.