EFFECT OF MODULATORS OF THE ADENYLATE-CYCLASE SYSTEM ON SWEET ELECTROPHYSIOLOGICAL TASTE RESPONSES IN GERBIL

The adenylate cyclase system has been implicated in sweet taste transd uction. The purpose of this study was to determine whether application of modulators of the adenylate cyclase system to the tongue alters sw eet taste responses. Integrated chorda tympani (CT) recordings were ma de in gerbils to sweet tastants before and after a 4-min application o f four types Of modulators of the adenylate cyclase system. The four t ypes of modulators tested were: a) NaF, a compound that promotes disso ciation of GTP-binding protein; b) forskolin, a powerful stimulant of adenylate cyclase; c) 8-bromoadenosine 3' : 5'-cyclic monophosphate so dium salt (8BrcAMP) and N-6,2'-O-dibutyryladenosine 3':5'-cyclic monop hosphate sodium salt (DBcAMP), two membrane permeable forms of cAMP; a nd d) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride ( H-7) and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide dihydrochl oride) (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), s odium 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 KCI (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. NaCl (20 mM), which was used a s a control for NaF, did not significantly enhance any of the response s when applied as a rinse. 8BrcAMP (1.16 mM) enhanced 30 mM sucrose by 16%, 300 mM glucose by 36%, 300 mM maltitol by 18%, and 6.5 mM D-tryp tophan by 24%. DBcAMP had a minimal effect on most of the compounds te sted with a 26% enhancement of 300 mM mannitol and a 17% blockage of 3 00 mM KCl. H-7 (300 mu M) enhanced 30 mM sucrose and 1.75 mM dulcin, b ut this may not be due to an effect on the adenylate cyclase system. H -8 (147 mu M) was used in a single trial with no consistent changes. T hese data indicate that modulation of the adenylate cyclase system can increase the intensity of some sweet taste responses.