Interaction between prostaglandin E1 and forskolin in modulation of cyclic AMP levels in rat epididymal adipocytes.

The interaction between the diterpene, forskolin and prostaglandin E1 on cAMP levels in isolated adipocytes of the rat was examined. Various doses of Prostaglandin E1 in the presence of 1-methyl-3-isobutylxanthine (2 mM) blocked the increase in the intracellular level of cAMP elicited by forskolin (0.1 microM or 5 microM). Interestingly, in the absence of 1-methyl-3-isobutylxanthine (or an adenosine blocker), or in the presence of 1-methyl-3-isobutylxanthine (2 mM) and forskolin (30 microM), prostaglandin E1 (1 nM-100 microM) exhibited biphasic dose-response kinetics. The stimulatory effect of PGE1 (greater than 1 microM) in presence of forskolin (30 microM) may be a consequence of prostaglandin receptor modification following endogeneous release of adenosine and prostaglandins by adipocytes stimulated to high levels of cAMP accumulation due to 30 microM forskolin.