The human parotid gland secretes much of the bicarbonate that enters the mouth. Prompted by studies of animal models, this study sought evidence for the expression of a functional Na+-HCO3- cotransporter (NBC) in human parotid acinar cells. Microfluorometric measurements of intracellular plc in isolated acini showed that the recovery from an acid load was achieved in part by HCO3- uptake via a Na+-dependent, DIDS-sensitive mechanism. By reverse transcriptase-polymerase chain reaction, a full-length NBCl clone was obtained showing more than 99%, homology with the human pancreatic isoform hpNBCl. Expressed in Xenopus oocytes, the electrogenicity of the transporter was detected as an inwardly directed, Na+- and HCO3--dependent flux of negative charge. Immunohistochemistry using antibodies raised to NBCl showed strong staining of the basolateral membrane of the acinar cells. Therefore, it was concluded that a functional electrogenic Na+-HCO3- cotransporter is expressed in the human parotid gland, and that it contributes to pH regulation in the acinar cells and could play a significant part in salivary secretion. (C) 2002 Elsevier Science Ltd. All rights reserved.