The role of intracellular cAMP and Ca(2+) in the excitation and adaptation of taste responses by HCl was investigated by direct measurement of intracellular pH (pH(i)) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) nerve recordings. Stimulating the tongue with HCl concentrations between 1 and 30 mM caused a dose-dependent increase in CT responses that were insensitive to voltage clamp of the lingual receptive field and to amiloride. At a fixed HCl concentration (20 mM) topical lingual application of 8-chlorophenylthio(CPT)-cAMP increased the magnitude of HCl-induced CT response by twofold under zero current clamp. The magnitude of the CT response increased further at -60 mV and decreased at +60 mV lingual voltage clamp but remained amiloride insensitive. In untreated polarized TRCs, apical stimulation with HCl concentrations between 1 and 30 mM HCl induced sustained decreases in TRC pH(i). The magnitude of pH(i) decrease increased with increasing HCl concentration. Following treatment of the basolateral membrane with 8-CPT-cAMP the decrease in pH(i) due to apical 1 mM HCl application was significantly increased. Treatment with cAMP alone decreased resting TRC pH(i) and inhibited the recovery of pH(i) from a basolateral NH4Cl pulse by 46%. Topical lingual application of ionomycin, a Ca(2+) ionophore, did not affect the initial CT response to 20 mM HCl +10 mM CaCl2, but the response declined rapidly to 50% of its initial level within 2 min. In polarized TRCs, basolateral exposure to ionomycin increased TRC pH(i) and activated pH(i) recovery from NH4Cl pulse by 388%. Apical HCl stimulation induced a transient decrease in resting TRC pH(i) followed by spontaneous recovery. The data suggest that cAMP enhances the sour taste of strong acids by activating a Ca(2+)- and amiloride-insensitive H(+) conductance and inhibiting pH(i) recovery in TRCs. However, an increase in [Ca(2+)]i stimulates pH(i) recovery, which, in turn, increases sensory adaptation to acids.