[3H]forskolin binding to cardiac adenylate cyclase in guinea pigs chronically infused with isoproterenol.

Guinea pigs were infused with the beta-adrenoceptor agonist isoproterenol (400 micrograms/kg/hr, 7 days) and cardiac adenylate cyclase was detected using [3H]forskolin. Two populations of [3H]forskolin binding sites were present in heart, the affinities (KD 2 nM and 280 nM) and densities (Bmax 9 and 900 fmol/mg protein) of which were unchanged by isoproterenol infusion compared with vehicle (1 mM HCl). The autoradiographic localisation of [3H]forskolin binding was also unchanged. The G protein activators NaF 10 mM and 5'-guanylylimidodiphosphate (Gpp(NH)p) 10 microM increased [3H]forskolin binding in heart from vehicle-treated animals by 100% and 80% respectively. NaF-stimulated binding was unchanged in isoproterenol-treated animals, however, Gpp(NH)p-stimulated binding was reduced by 35% which may indicate an increased influence of Gi.