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Updated: Aug 9, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Inhibition of [3H]forskolin binding by Gpp[NH]p may reflect adenylyl cyclase coupling to Gi
A García-Jiménez1, R F Cowburn, B Einblad
1Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, KFC Novum, Huddinge, Sweden.
Abstract:
The effect of the GTP-analogue guanylyl 5'-imidodiphosphate (Gpp[NH]p) on [3H]forskolin binding was studied in rat brain using autoradiography. In the striatum, 100 microM Gpp[NH]p produced a 40% increase in binding, whereas a decrease of about 30% was observed with low Gpp[NH]p concentrations (0.1-1 microM). In the molecular layer of the cerebellum all concentrations of Gpp[NH]p decreased [3H]forskolin binding. The decrease in binding disappeared in both striatum and the molecular layer of cerebellum in sections pretreated with 100 microM N-ethylmaleimide (NEM) for 10 min. NEM pretreatment did not significantly affect the stimulation of [3H]forskolin binding by micromolar concentrations of Gpp[NH]p in the striatum, but reversed the decrease observed in the molecular layer of the cerebellum, to an increase. Based on these data we suggest that the effects of the GTP-analogue Gpp[NH]p on [3H]forskolin binding may involve both Gs and Gi, where a stimulation produces an increase and decrease in binding respectively. The regional effects of Gpp[NH]p may reflect differences in the responsiveness of adenylyl cyclase to Gs and Gi-mediated effects.
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