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.
Choi
S-Y
SY
Department of Physiology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Li
J
J
Jo
S-H
SH
Lee
S J
SJ
Oh
S B
SB
Kim
J-S
JS
Lee
J-H
JH
Park
K
K
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D002460:Cell Line; D003891:Desipramine / Q000009:adverse effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014987:Xerostomia / Q000139:chemically induced*
D000929:Antidepressive Agents, Tricyclic; D017923:Sodium-Hydrogen Exchangers; D003891:Desipramine