The adenylate cyclase system has been implicated in sweet taste transduction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alters sweet taste responses. Integrated chorda tympani (CT) recordings were made in gerbils to sweet tastants before and after a 4-min application of four types of modulators of the adenylate cyclase system. The four types of modulators tested were: a) NaF, a compound that promotes dissociation of GTP-binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' :5'-cyclic monophosphate sodium salt (8BrcAMP) and N6,2'-O-dibutyryladenosine 3' :5'-cyclic monophosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; and d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochloride) (H-8), which are protein kinase inhibitors. The sweet compounds tested were: sucrose (30 mM and 100 mM), glucose (300 mM), fructose (300 mM), maltitol (150 mM and 300 mM), mannitol (300 mM and 500 mM), sodium saccharin (10 mM), D-tryptophan (6.5 mM), dulcin (0.88 mM, 1.75 mM, and 3.5 mM), and stevioside (0.55 mM and 1.1 mM). NaCl (30 mM and 100 mM) and KCl (300 mM and 500 mM) were used as control stimuli. The main findings were as follows. Application of NaF (20 mM) for 4 min as a rinse significantly enhanced all of the sweet compounds by at least 23%, except for 10 mM sodium saccharin and 6.5 mM D-tryptophan, while all control compounds were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)