Stimulation of cAMP accumulation and lipolysis in hamster adipocytes with forskolin

This study compares the effects of forskolin and isoproterenol on lipolysis and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in hamster white adipocytes. Rates of lipolysis in forskolin-stimulated cells were equivalent to those in cells incubated with isoproterenol, but cAMP levels were more than 10-fold greater in the presence of forskolin. The stimulatory effects of forskolin were partially inhibited by N6-phenylisopropyl adenosine but not by 2',5'-dideoxyadenosine. In other experiments, cells were exposed to forskolin in combination with either isoproterenol or adenosine deaminase. A concentration of forskolin that caused only a small increase in lipolysis was used. When isoproterenol or adenosine deaminase were added with forskolin, lipolysis increased dramatically, but cAMP content either did not change, as occurred with isoproterenol, or increased only slightly with adenosine deaminase. Isoproterenol potentiation of forskolin's lipolytic action persisted in the absence of extracellular K+, even though the lipolytic response to isoproterenol alone was absent in K+-free media. These data demonstrate that the lipolytic responses of adipose tissue are more complex than are responses simply in proportion to cellular concentration of cAMP. Such complexity could arise if lipolytic regulatory factors other than cAMP existed or if cAMP and protein kinase were functionally segregated within adipocytes.