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

Abstract

Objective: Dopamine (DA) has been proposed to act as a modulator of GI motility, via activation of specific receptors D1- and D2-like receptors widely expressed throughout the length of the gastrointestinal tract, in different animal species. However, little and not clear information are available about DA effect in the human gut. The aims of this study were to elucidate whether dopamine may affect contractility in human colon, the receptor subtypes involved and the possible differences in the function and distribution of dopaminergic receptors between longitudinal and circular muscle. Methods: Mechanical responses to dopamine were examined in vitro as changes in isometric tension in strips of circular and longitudinal muscle layers from human colon. Results: In the circular muscle DA (1–300 lM) induced a concentration-dependent contraction, reduced by SCH 23390, D1-like receptor antagonist, and mimicked by SKF 38393, D1-like receptor agonist, but not modified by domperidone D2-like receptor antagonist. The neural blocker TTX or the muscarinic antagonist atropine did not affect D1-like mediated contraction. In contrast in the longitudinal muscular strips DA (1–300 lM) caused a concentration-dependent relaxation. The inhibitory effect was antagonized by domperidone, D2-like receptor antagonist, and mimicked by bromocriptine, D2-like receptor agonist, but unaffected by SCH 23390 D1-like receptor antagonist. The D2-like mediated relaxation was TTX-insensitive and unaffected by blocking the nitrergic pathway. Conclusion: DA in human colon induces opposite effects mediated by different classes of receptors. specific dopaminergic receptors. DA causes contraction in the circular muscle layers via excitatory D1-like receptors, located at postjunctional level. Indeed, relaxation on longitudinal muscle is mediated via inhibitory D2- like receptors. Since during the intestinal peristalsis, longitudinal muscle contracts and relaxes in reverse fashion to circular muscle, the opposite effect of DA on the muscular layers may contribute to the modulation of peristaltic reflex.