Activation of phospholipase A2 by the human endothelin receptor in Chinese hamster ovary cells involves Gi protein-mediated calcium influx.
The signalling pathways used by the human endothelin A receptor to activate phospholipase A2 in Chinese hamster ovary cells were investigated. Pertussis toxin caused a partial but significant reduction in endothelin-1-induced arachidonic acid release although cAMP-dependent kinase inhibitors did not mimic its action. Extracellular calcium and its entry into the cell was essential for activation of phospholipase A2 as its removal from media or incubation with an intracellular calcium chelator-reduced activation. Nifedipine had no effect on endothelin-1-induced arachidonic acid release while divalent cations caused a significant reduction indicating the possible role of CRAC. Thapsigargin caused an increase in arachidonic acid release which was completely inhibited by pertussis toxin treatment. This further supports the involvement of CRAC in calcium influx and activation of phospholipase A2 by the human endothelin A receptor.
Department of Biological Sciences, University of Paisley, Scotland.
H
H
Kruger
S
S
Carr
J C
JC
Brennand
J S
JS
McLean
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001693:Biological Transport, Active; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D017466:Receptors, Endothelin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D016232:Endothelins; D017466:Receptors, Endothelin; D011994:Recombinant Proteins; D013729:Terpenes; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D019284:Thapsigargin; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; D009543:Nifedipine; D002118:Calcium