We investigated whether differences in binding sites for [3H]forskolin could account for the low potency of forskolin on adenylate cyclase (EC 4.6.1.1) from rat lung compared with heart or liver adenylate cyclase. Forskolin (0.1 mM) increased basal adenylate cyclase activity 41-fold in heart, 27-fold in liver, but only 3-fold in lung. The low potency in lung could not be accounted for by any lack of enzyme or stimulatory nucleotide-binding protein, since sodium fluoride (10 mM) increased basal activity 9-12-fold in all three tissues. The effectiveness of forskolin on adenylate cyclase appears to be related to the presence of specific [3H]forskolin binding sites. [3H]Forskolin binding in both heart and liver membranes was consistent with single binding sites with dissociation constants of 0.74 +/- 0.25 microM and 1.43 +/- 0.21 microM respectively. No such binding sites were detected in lung membranes. The binding was of low affinity (greater than 100 microM) and showed no tendency to saturate. These results are not consistent with the hypothesis that the nucleotide-binding protein influences stimulation of adenylate cyclase by forskolin, rather [3H]forskolin binding sites appear to be an important determinant of the effect of forskolin in different tissues.
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