The interaction between the diterpene, forskolin and prostaglandin E1l on cAMP levels in isolated adipocytes of the rat was examined. Various doses of Prostaglandin E1 in the presence of 1-methyl-3-isobutyl xanthine (2 mM) blocked the increase in the intracellular level of CAMP elicited by forskolin (0.1 PM or 5 PM). 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 PM), prostaglandin E1 (1 nM-100 μM) exhibited biphasic dose-response kinetics. The stimulatory effect of PGE1 (> 1 μM) in presence of forskolin (30 μM 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 PM forskolin.
Bibliographical noteFunding Information:
I am grateful to Drs. Kay and J.J.M. Bergeron of McGill University for their critical review of this manuscript. I am thankful to Mrs. Sandy Wehmann for typing of the manuscript. This work was performed at the Laboratories of Cyclic Nucleotide Research, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston and was supported by grant no. AM 27198 from the National Institute of Health.