Forskolin stimulation of cyclic AMP accumulation in rat brain cortex slices is markedly enhanced by endogenous adenosine.

: Stimulation of cyclic AMP (cAMP) accumulation in rat cortex slices by 1 μM forskolin (F) was markedly reduced (96%) by treatment with adenosine deaminase (ADA). The effect of ADA was progressively less at higher concentrations of F, but still inhibited the response by 50% at 100 μM F. ADA-mediated inhibition of the cAMP response to 1 μM F was completely reversed by 5 μM 2-chloroadenosine (CA), an ADA-resistant analogue. Stimulation by F (controls) and F plus CA (ADA treated) in cortex slices was significantly inhibited by 200 μM caffeine (CAF) and by 10 μM 8-phenyltheophylline. cAMP accumulation in ADA-treated cortex slices stimulated with CA at concentrations from 5 to 100 μM was markedly enhanced by 1 μM F. Neither ADA treatment nor 200 μM CAF significantly affected cAMP accumulation in slices stimulated by 1 μM vasoactive intestinal polypeptide or adenylate cyclase in membranes stimulated by 1 μM F. CAF (1 mM) did not significantly increase basal cAMP levels in cortex slices, whereas 1 mM 3-isobutyl-1-methylxanthine caused a significant 80% increase and 100 μM rolipram enhanced cAMP levels by 4.5-fold. F-stimulated cAMP accumulation (1 μM) in cortex slices was inhibited 98% by 1 mM CAF and 49% by 1 mM 3-isobutyl-1-methylxanthine, and was enhanced 2.5-fold by 100 μM rolipram. These data have been interpreted to indicate that the stimulation of cAMP accumulation in rat cortex slices by 1 μM F is predominantly due to synergistic interaction with endogenous adenosine and that the inhibition of this response by CAF is largely due to blockade of adenosine receptors.