Stimulation of intracellular Ca2+ oscillations by diacylglycerol in human myometrial cells.
Stimulation of G-protein coupled membrane receptors linked to phospholipase C results in production of the second messengers diacylglycerol and inositol-1,4,5-trisphosphate (IP3). IP3 releases Ca2+ from the endoplasmic reticulum, which triggers increased Ca2+ influx across the plasma membrane, so-called capacitative calcium entry. DAG can also activate plasma membrane calcium-permeable channels but the mechanism is still not fully understood. In the pregnant human myometrial cell line PHM1 and in primary myometrial cells, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeant analogue of diacylglycerol, induced variable oscillatory patterns of intracellular free Ca2+. Similar behavior was seen with Sr2+ entry. The Ca2+ oscillations were not blocked by a broad spectrum of protein kinase C inhibitors, including chelerytrine, bisindolylmaleimide I and calphostin C, and were enhanced and prolonged by RHC-80267, an inhibitor of diacylglycerol lipase. The OAG-induced oscillatory response was not dependent on Ca2+ release from the endoplasmic reticulum but required extracellular Ca2+. Our results indicate that diacylglycerol directly activates cation channels in PHM1 and primary myometrial cells and promotes intracellular Ca2+ oscillations by actions independent of intracellular Ca2+ -ATPase activity and protein kinase C involvement.
Shlykov
Sergiy G
SG
Department of Biomedical Sciences, Colorado State University, Fort Collins 80523-1680, USA.
Sanborn
Barbara M
BM
D002118:Calcium / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013997:Time Factors
D004075:Diglycerides; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D008071:Lipoprotein Lipase; D002118:Calcium