Novel evidences for a role of dopamine as modulator of intestinal motility: a study on mouse distal colon

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Ithas been classically considered that the pathological hallmarks of PD affect primarily the substantia nigra.Nevertheless, it has become increasingly evident that PD is a multicentric neurodegenerative process thataffects several neuronal structures outside the substantia nigra, among which is the enteric nervous system(ENS). Pathological alterations within the ENS could be involved in the gastrointestinal (GI) dysfunctionfrequently encountered by PD patients. Dopamine (DA) seems to be a major candidate for the impairmentof GI function in PD since its levels were found to be decreased in the ascending colon from PD patients.However, the effective role of DA, and of its receptors, in the modulation of GI functions is far from beingclear. Thus, the aim of this study was to explore the role of DA in the GI tract, using as model the mousedistal colon, analyzing, in vitro, spontaneous and neurally-evoked mechanical activity of the circular muscle.DA caused a direct inhibitory effect on the colonic spontaneous contractions, antagonized by SCH-23390, D1receptor antagonist, and by domperidone, D2 receptor antagonist. In addition, DA induced a significantdecrease in the amplitude of the neurally-evoked cholinergic contractions, affected by SCH-23390 and by LNAME,nitric oxide (NO) synthase inhibitor, but not by domperidone. SCH-23390 per se increased theamplitude of both spontaneous and neurally-evoked cholinergic contractions. In conclusion, in mouse distalcolon, dopamine is a negative modulator of GI motility via activation of D1 and D2 receptors. Both receptorsare available for pharmacological recruitment, even if only D1-like receptors appear to be preferentiallystimulated by endogenous DA. D1 receptors slow down the mouse colonic motility, reducing acetylcholinerelease from ENS via a NO-dependent pathway.
Original languageEnglish
Number of pages2
Publication statusPublished - 2014

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