The neurotransmitters dopamine and serotonin control the peristaltic movement of the gut
that consists of propagating waves of rhythmic contraction and relaxation. While intestinal cells of
Cajal (ICC) serve as a pacemaker in the gut, the effect of dopamine on the pacemaker activity of ICC
remains unknown. Here, we report that together with serotonin receptors, the dopamine receptor D₂
contributes to maintaining [Ca²⁺]i oscillations in ileum ICC. When the antagonist for the D₂ receptor
was applied to the cell cluster or the tissue culture prepared from muscle layers of the mouse small
intestine, the amplitude of [Ca²⁺]i oscillations in ICC declined after a transient increase. On the other
hand, treatment with the D₂ receptor agonist decreased the frequency of [Ca²⁺]i oscillations in ICC.
These results suggest that basal level activity of the D₂ receptor is crucial for maintaining [Ca²⁺]i
oscillations in ICC. The decrease in the [Ca²⁺]i oscillation amplitude upon the D₂ receptor antagonist
treatment was abrogated by antagonizing the serotonin receptor 5HT₂, indicating an inhibitory effect
of the 5HT₂ receptor on the [Ca²⁺]i oscillations. Together with the finding that treatment with the
antagonist for the serotonin receptor 5HT₃ completely eliminated [Ca²⁺]i oscillations in ICC, our
results show that dopamine and serotonin receptors cooperatively regulate pacemaker activity of
ICC.