The role of basolateral Na(+)-H(+) exchanger isoform-1 (NHE-1) was investigated in neural adaptation of rat taste responses to acidic stimuli, by direct measurement of intracellular pH (pH(i)) in polarized taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. In TRCs perfused with CO(2)/HCO(3)(-)-free solution (pH 7.4), removal of basolateral Na(+) decreased pH(i) reversibly and zoniporide, a specific NHE-1 blocker, inhibited the Na(+)-induced changes in pH(i). The spontaneous rate of TRC pH(i) recovery from NH(4)Cl pulses was inhibited by basolateral zoniporide with a K(i) of 0.33microm. Exposure to basolateral ionomycin, reversibly increased TRC Ca(2+), resting pH(i), and the spontaneous rate of pH(i) recovery from an NH(4)Cl pulse. These effects of Ca(2+) on pH(i) were blocked by zoniporide. In in vivo experiments, topical lingual application of zoniporide increased the magnitude of the CT responses to acetic acid and CO(2), but not to HCl. Topical lingual application of ionomycin did not affect the phasic part of the CT responses to acidic stimuli, but decreased the tonic part by 50% of control over a period of about 1 min. This increased adaptation in the CT response was inhibited by zoniporide. Topical lingual application of 8-CPT-cAMP increased the CT responses to HCl, but not to CO(2), and acetic acid. In the presence of cAMP, ionomycin increased sensory adaptation to HCl, CO(2), and acetic acid. Thus, cAMP and Ca(2+) independently modulate CT responses to acidic stimuli. While cAMP enhances TRC apical H(+) entry and CT responses to strong acid, an increase in Ca(2+) activates NHE-1, and increases neural adaptation to all acidic stimuli.