Previous studies have shown that local anesthetics block voltage-dependent Na+ channels and nicotinic acetylcholine receptors. The present study investigated the effect of the local anesthetic, procaine on another ligand-gated ion channel, the 5-HT3 receptor, in rat nodose ganglion neurons. Procaine (0.01-100 microM) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. The inhibition was fully reversible, concentration-dependent but not sensitive to changes in membrane potential. Concentration-response curves indicated that procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM. These observations suggest that one of the actions of procaine in nervous system is on 5-HT3 receptors.