ACTIVATION OF PHOSPHOLIPASE A(2) BY THE HUMAN ENDOTHELIN RECEPTOR IN CHINESE-HAMSTER OVARY CELLS INVOLVES G(I) PROTEIN-MEDIATED CALCIUM INFLUX

The signalling pathways used by the human endothelin A receptor to activate phospholipase A(2) 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 A(2) 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 A(2) by the human endothelin A receptor. (C) 1995 Academic Press, Inc.