7-Chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) is a specific inhibitor of mitochondrial Na+/Ca2+ exchanger and also inhibits Ca2+-ATPase. As mitochondria controls Ca2+ signaling, mitochondrial Na+/Ca2+ exchanger might play an important role in the secretory process in salivary glands. Clinical data shows that mouth dryness (xerostomia) can be mediated through the altered Na+/Ca2+ exchanger function. However, the role of Na+/Ca2+ exchanger in the submandibular salivary gland function remains unclear. To study the effect of CGP-37157 on salivary cells function, we analysed in vivo parameters of salivation: saliva flow rate and electrolyte content (Ca2+, P2+, Na+). Rats were anesthetised by ketamine (90 mg/kg) and fixed in the supine position. To collect whole saliva two ducts of submandibular gland were cannulated. Saliva, that secreted over a period of 5 min, was collected in a tube after the tested substances were injected into gland lobes. Saliva flow rate was calculated as a volume of saliva secreted per 5 min normalised to the animal weight/hour. Concentration of electrolytes was measured: Ca2+ – o-cresol-phtalein method; P2+ – UV detection, and Na+ – flame emission spectroscopy. We showed that CGP-37157 (5 µM) after an intraglandular injection decreased saliva flow rate, which reached its lowest level at 25 min after drug injection (59.9±6.7%, P<0.001, n=7). As expected, administration of carbachol (Ch, 5 µM) increased saliva flow rate (283.1±65.4%, P<0.05, n= 5). In addition, we established, that CGP-37157 caused a significant reduction of saliva flow rate and subsequent injection of Ch (at 20 min of experiment) increased saliva flow rate and reached a peak at 25 min of the experiment (46±4.4%, P<0.0001, n=6). However, the stimulation potency of Ch was much less pronounced (compare to the sole effect of Ch). We further found that application of CGP-37157, Ch and CGP-37157 in the mixture with Ch significantly changed Ca2+, P2+ and Na+ concentrations in the final saliva. In particular, the concentration of Ca2+ decreased: CGP-37157 – 20.8±0.9% (P<0.0001, n = 3), Ch – 36.7±0.5% (P<0.0001, n=3), CGP-37157 in the mixture with Ch – 36.1±0.7% (P<0.001, n=3). Similarly, Ch (5 µM) and CGP-37157 in the mixture with Ch decreased of P2+ concentration: Ch – by 20±3.3% (P<0.001, n=3), CGP-37157 in the mixture with Ch – by 52.6±4.1% (P<0.001, n=3), but in case of sole CGP-37157, we observed an increase of P2+ concentration – by 16±8.3% (P<0.001, n = 3). Contrary to the Ca2+ and P2+, CGP-37157 caused an increase of Na+ concentration – 290.7±13.1% (P>0.0001, n=4) and Ch – 81.2±3% (P<0.05 n=3). At the same time, no significant changes were observed upon injection of CGP-37157 in the mixture with Ch. We suggest that mitochondrial Na+/Ca2+ exchanger is directly involved in the regulation of functioning in the submandibular gland.