title: Inhibition of [3H]forskolin binding by Gpp[NH]p may reflect adenylyl cyclase coupling to Gi.
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.
authors.affiliation: Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, KFC Novum, Huddinge, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: García-Jiménez
authors.forename: R F
authors.initials: RF
authors.lastname: Cowburn
authors.forename: B
authors.initials: B
authors.lastname: Einblad
authors.forename: J
authors.initials: J
authors.lastname: Fastbom
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002531:Cerebellum / Q000737:chemistry; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
chemical_list: D004791:Enzyme Inhibitors; D014316:Tritium; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D005033:Ethylmaleimide