Mice lacking the dopamine transporter display altered regulation of distalcolonic motility

The mechanisms by which dopamine (DA) influences gastrointestinal (GI) trac t motility are incompletely understood and complicated by tissue- and speci es-specific differences in dopaminergic function. To improve the understand ing of DA action on GI motility, we used an organ tissue bath system to cha racterize motor function of distal colonic smooth muscle segments from wild -type and DA transporter knockout (DAT -/-) mice. In wild-type mice, combin ed blockade of D-1 and D-2 receptors resulted in significant increases in t one (62 +/- 9%), amplitude of spontaneous phasic contractions (167 +/- 24%) , and electric field stimulation (EFS)-induced (40 +/- 8%) contractions, su ggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were low er in DAT -/- mice relative to wild-type mice. These differences were elimi nated by combined D-1 and D-2 receptor blockade, indicating that the inhibi tory effects of DA on distal colonic motility are potentiated in DAT -/- mi ce. Motility index was decreased but spontaneous phasic contraction frequen cy was enhanced in DAT -/- mice relative to wild-type mice. The fact that s pontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon.