Desipramine inhibits Na+/H+ exchanger in human submandibular cells

A common and significant side-effect of the antidepressant desipramine is xerostomia (dry mouth). We investigated the effect of desipramine on Na(+)/H(+) exchanger, which is an important modulator of salivary secretion. In dissociated human submandibular acinar cells, desipramine inhibited intracellular pH recovery in a concentration-dependent manner. Likewise, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a Na(+)/H(+) exchanger inhibitor, had the same effect as desipramine, whereas the effect of 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), a Na(+)/HCO(3)(-) co-transporter inhibitor, was not dramatic. Although desipramine is known to inhibit catecholamine re-uptake, desipramine also inhibited pH recovery in the human submandibular gland cell line, HSG cells, which lack nerve inputs. Our results suggest that desipramine directly inhibits Na(+)/H(+) exchange in human submandibular glands without the involvement of catecholamine re-uptake, revealing the cellular mechanism of desipramine-evoked xerostomia.