Opposite effects of dopamine on the mechanical activity of longitudinal and circular muscles in human colon

Objective: Dopamine (DA) has been proposed to act as amodulator of GI motility, via activation of specificreceptors D1- and D2-like receptors widely expressedthroughout the length of the gastrointestinal tract, indifferent animal species. However, little and not clearinformation are available about DA effect in the humangut. The aims of this study were to elucidate whetherdopamine may affect contractility in human colon, thereceptor subtypes involved and the possible differencesin the function and distribution of dopaminergic receptorsbetween longitudinal and circular muscle.Methods: Mechanical responses to dopamine wereexamined in vitro as changes in isometric tension instrips of circular and longitudinal muscle layers fromhuman colon.Results: In the circular muscle DA (1–300 lM) induced aconcentration-dependent contraction, reduced by SCH23390, D1-like receptor antagonist, and mimicked bySKF 38393, D1-like receptor agonist, but not modified bydomperidone D2-like receptor antagonist. The neuralblocker TTX or the muscarinic antagonist atropine didnot affect D1-like mediated contraction. In contrast inthe longitudinal muscular strips DA (1–300 lM) causeda concentration-dependent relaxation. The inhibitoryeffect was antagonized by domperidone, D2-like receptorantagonist, and mimicked by bromocriptine, D2-likereceptor agonist, but unaffected by SCH 23390 D1-likereceptor antagonist. The D2-like mediated relaxationwas TTX-insensitive and unaffected by blocking thenitrergic pathway.Conclusion: DA in human colon induces oppositeeffects mediated by different classes of receptors. specificdopaminergic receptors. DA causes contraction inthe circular muscle layers via excitatory D1-like receptors,located at postjunctional level. Indeed, relaxationon longitudinal muscle is mediated via inhibitory D2-like receptors. Since during the intestinal peristalsis,longitudinal muscle contracts and relaxes in reversefashion to circular muscle, the opposite effect of DA onthe muscular layers may contribute to the modulationof peristaltic reflex.