Dopamine and Serotonin Receptors Cooperatively Modulate Pacemaker Activity of Intestinal Cells of Cajal

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.