Mice lacking the dopamine transporter display altered regulation of distal colonic motility.
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 smooth muscle segments from wild-type and DA transporter knockout (DAT -/-) mice. In wild-type mice, combined blockade of D(1) and D(2) receptors resulted in significant increases in tone (62 +/- 9%), amplitude of spontaneous phasic contractions (167 +/- 24%), and electric field stimulation (EFS)-induced (40 +/- 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 -/- 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 -/- mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT -/- 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.
Walker
J K
JK
Howard Hughes Medical Institute, Departments of Cell Biology and Medicine, Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA.
Gainetdinov
R R
RR
Mangel
A W
AW
Caron
M G
MG
Shetzline
M A
MA
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000737:chemistry* / Q000502:physiology*; D004298:Dopamine / Q000032:analysis / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D011189:Potassium Chloride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D002352:Carrier Proteins; D018679:Cholinergic Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; C493215:Slc6a3 protein, mouse; D011189:Potassium Chloride; D013469:Sulpiride; D002217:Carbachol; D004298:Dopamine