Bombesin stimulates the rapid activation of phospholipase A2-catalyzed phosphatidylcholine hydrolysis in Swiss 3T3 cells.
In Swiss 3T3 fibroblasts bombesin stimulated the release of arachidonic acid in a time- and dose-dependent manner. Arachidonate levels were significantly elevated after only a 2-s stimulation with the agonist. Furthermore, by measuring the arachidonate content of cellular phospholipids after cell activation, it was shown that there was selective depletion from phosphatidylcholine over the same time course. The corresponding production of lysophosphatidylcholine suggested the involvement of a phosphatidylcholine-specific phospholipase A2. Initial arachidonic acid release was not dependent on the presence of extracellular calcium, not activated by treatment of the cells with thapsigargin, and was unaffected by down-regulation of protein kinase C activity, or by treatment of the cells with the protein kinase C inhibitor staurosporine. These data strongly suggest that occupation of the bombesin receptor is closely coupled to activation of phospholipase A2 which results in the rapid release of arachidonic acid from phosphatidylcholine.
Currie
S
S
Department of Biochemistry, University of Glasgow, United Kingdom.
Smith
G L
GL
Crichton
C A
CA
Jackson
C G
CG
Hallam
C
C
Wakelam
M J
MJ
D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006868:Hydrolysis; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin
D000470:Alkaloids; D002250:Carbon Radioisotopes; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D010743:Phospholipids; D013729:Terpenes; D016718:Arachidonic Acid; D019284:Thapsigargin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D000252:Calcium-Transporting ATPases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin; D002118:Calcium