Role for D1-like and D2-like dopamine receptors in the modulation of intestinal motility in mice

Abstract

Objective: In the last years a plethora of studies addressed dopamine (DA) as a modulator within the enteric nervous system (ENS), controlling gastrointestinal (GI) functions via activation of D1- and D2-like receptors. However, the effective role and functional significance of DA in the ENS, and the contribution of its receptors, are still a matter of debate. Pathological alterations of dopaminergic system in the gut may be likely implicated in different motor GI disorders, including dyspepsia and gastroparesis. Thus, a detailed characterization of the enteric dopaminergic signalling is necessary. The aim of this study was to explore the role of DA in the GI tract, using as model the mouse distal colon. Methods: Spontaneous and neurally-evoked mechanical activity of colonic circular muscle strips were investigated via organ bath technique. Results: DA (1–300 lM) caused a tetrodotoxin-insensitive inhibitory effect on the colonic spontaneous contractions, mimicked by bromocriptine, D2-like receptor agonist, and antagonized by domperidone, D2-like receptor antagonist. In addition, DA (3 lM) significantly reduced the amplitude of neurally-evoked cholinergic contractions, without affecting the direct smooth muscle cholinergic contractions elicited by carbachol. DA inhibitory effect was mimicked by SKF-38390, D1-like receptor agonist, and antagonized both by SCH-23390, D1-like receptor antagonist, and by L-NAME, nitric oxide (NO) synthase inhibitor. SCH-23390 per se increased the amplitude of neurally-evoked cholinergic contractions. Conclusion: DA is a negative modulator of colonic motility via activation of D1- and D2-like receptors. Although both receptors are available for pharmacological recruitment, only D1-like receptors located on enteric neurons appear to be activated by endogenous DA. D1-like receptors activation exerts a basal inhibitory control on colonic motility, reducing acetylcholine release from ENS via a NO-dependent pathway.