cAMP dependent inhibition of thromboxane A2, prostacyclin and PGF2α synthesis in mouse hepatocytes

The role of cAMP dependent regulation in thromboxane A₂, prostacyclin and PGF_2α synthesis (measured by radioimmunoassay) was investigated in isolated mouse hepatocytes and in microsomal membranes prepared from these cells. In isolated hepatocytes N⁶,O²-dibutyryl cAMP inhibited the formation of all the three derivatives, while calcium ionophore A 23187 stimulated their synthesis. Addition of the dissociated catalytic subunit of cAMP dependent protein kinase and ATP to microsomal membranes inhibited the production of TXA₂, PGI₂ and PGF_2α by about 50% and this inhibition was counteracted by the combined addition of heat stable inhibitor protein of cAMP dependent protein kinase. It is concluded that in parenchylmal liver cells cAMP dependent phosphorylation is directly involved in the inhibition of prostanoid synthesis.