Receptor Mediated Activation of Phospholipase A2: Arachidonic Acid and its Metabolites as Second Messengers

  • Julius Axelrod
  • Ronald M. Burch
  • Carole L. Jelsema
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)


GTP binding proteins, called G or N proteins, are involved in receptor-mediated signal transduction in cells. Certain GTP binding proteins, NS or Ni, have been shown to cause the activation or inhibition, respectively, of adenylate cyclase (Rodbell, 1980).The transducing N proteins are heterotrimers consisting of α, β, and γ subunits (Gilman, 1984). When a ligand interacts with a membrane receptor, GDP, which is bound to the α subunit of the N protein, is replaced by GTP. This sets off a cascade of biochemical reactions in which the α subunit dissociates from the βγ subunit. The GTP-bound α subunit of NS then interacts with the adenylate cyclase to enhance conversion of ATP to cyclic AMP.This series of reactions is terminated by the ability of the α subunit to function as a GTPase to hydrolyze the bound GTP to GDP. When this happens the α subunit reassociates with the βγ subunit to terminate the reaction. The actions of the NSα subunit on adenylate cyclase can be prolonged by the addition of GTPγS, a GTP analogue that is only slowly hydrolyzed by GTPase. The stimulatory NSα can also be directly activated by cholera toxin which acts by ADP ribosylating the NSα subunit. This then stimulates adenylate cyclase to generate cyclic AMP.


Arachidonic Acid Pertussis Toxin Arachidonic Acid Release Inositol Triphosphate FRTL5 Cell 
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© The Wenner-Gren Center 1987

Authors and Affiliations

  • Julius Axelrod
  • Ronald M. Burch
  • Carole L. Jelsema

There are no affiliations available

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