Prostaglandin E₂ can bimodally inhibit and stimulate the epididymal adipocyte adenylyl cyclase activity

Measurements of prostaglandin E₂ (PGE₂)-induced adenylyl cyclase acivity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE₂ (<10 mM) and stimulation at higher concentrations. This biphasic effect of PGE₂ was obtained when adenylyl cyclase was stimulated with GTP or NaF. In the presence of forskolin only the inhibitory phase by PGE₂ was observed. Suplprostone, a PGE₂ analogue, did not affect cAMP synthesis in the presence of either GTP or NaF; however, in the presence of forskolin, it inhibited cAMP production similarly to PGE₂. Treatment of the membranes with cholera or pertussis toxin did not alter the biphasic effect of PGE₂ on cAMP production. These findings raise the possibility that PGE₂ acts through several receptor subtypes which are coupled to GTP binding proteins different from the classical Gi or Gs proteins.