Mice lacking the dopamine transporter display altered regulation of distal colonic motility. Am J Physiol Gastrointest Liver Physiol 279: G311-G318, 2000.-The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue-and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic

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... oth muscle segments from wild-type and DA transporter knockout (DAT Ϫ/Ϫ) mice. In wild-type mice, combined blockade of D 1 and D 2 receptors resulted in significant increases in tone (62 Ϯ 9%), amplitude of spontaneous phasic contractions (167 Ϯ 24%), and electric field stimulation (EFS)-induced (40 Ϯ 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT Ϫ/Ϫ mice relative to wild-type mice. These differences were eliminated by combined D 1 and D 2 receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT Ϫ/Ϫ mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT Ϫ/Ϫ mice relative to wild-type mice. The fact that spontaneous 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. transgenic mice; motility index; dopamine receptor antagonists; electric field stimulation; peripheral hyperdopaminergia GASTROINTESTINAL (GI) motility is modulated by a complex system of intrinsic and extrinsic nerves, circulating hormones, and locally produced mediators. One such modulator is dopamine (DA). A description of the effect of DA on GI motility is complicated for three main reasons. First, DA can produce both inhibitory and excitatory effects on GI motility (reviewed in Ref.