The Na+/Ca2+ exchanger (NCX) is a bidirectional transporter that is
controlled by membrane potential and transmembrane gradients of Na+ and
Ca2+. To reveal the functional role of NCX on gastrointestinal motility, we
have previously used NCX1 and NCX2 heterozygote knockout mice (HET). We found that NCX1
and NCX2 play important roles in the motility of the gastric fundus, ileum and distal
colon. Therefore, we believed that NCX1 and NCX2 play an important role in transport of
intestinal contents. Here, we investigated the role of NCX in a mouse model of
drug-induced diarrhea. The fecal consistencies in NCX1 HET and NCX2 HET were assessed
using a diarrhea induced by magnesium sulfate, 5-hydroxytryptamine (5-HT) and
prostaglandin E2 (PGE2). NCX2 HET, but not NCX1 HET, exacerbated
magnesium sulfate-induced diarrhea by increasing watery fecals. Likewise, 5-HT-induced
diarrheas were exacerbated in NCX2 HET, but not NCX1 HET. However, NCX1 HET and NCX2 HET
demonstrated PGE2 induced diarrhea similar to those of wild-type mice (WT). As
well as the result of the distal colon shown previously, in the proximal and transverse
colons of WT, the myenteric plexus layers and the longitudinal and circular muscle layers
were strongly immunoreactive to NCX1 and NCX2. In this study, we demonstrate that NCX2 has
important roles in development of diarrhea.