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

Abstract

The idea of a dopaminergic enteric transmission, independent of the sympathoadrenal system, has been proposed different years ago due to the observations that neurons, expressing both the dopamine (DA)-synthesizing enzyme and the dopamine transporter, but not the norepinephrine-synthesizing enzyme, were present within the enteric nervous system (ENS) in both animal models and humans. 1,2 DA seems to be implicated in several functions in GI tract, 3 activating specific receptors belonging to the G protein-coupled receptor family categorized in two main families: D1-like receptor (D1 and D5 receptors) and D2-like receptor(D2, D3, and D4 receptors), present from the stomach through the distal colon in different animal species. 2 Abstract Background: Because dopamine (DA) has gained increasing evidence as modulator of gut motility, we aimed to characterize dopaminergic response in human colon, evaluating function and distribution of dopamine receptors in circular vs longitudinal muscle strips. Methods: Mechanical responses to DA and dopaminergic agonists on slow phasic contractions and on basal tone were examined in vitro as changes in isometric tension. RT-PCR was used to reveal the distribution of dopaminergic receptors. Key Results: In spontaneous active circular muscle, DA induced an increase in the amplitude of slow phasic contractions and of the basal tone, via activation of D1-like receptors. DA contractile responses were insensitive to neural blockers or to atropine and inhibited by phospholipase C (PLC) pathway inhibitors. In precontracted circular muscle strips, DA, at the higher concentrations tested, caused a relaxant response via activation of D2-like receptors. In the longitudinal muscle, DA caused only muscular relaxation due to activation of D2-like receptors. DA relaxant responses were insensitive to neural blockers or to nitric oxide synthase inhibitor and reduced by a wide-spectrum K + channel blockers. Transcripts encoding for all the dopaminergic receptor subtypes was observed in both circular and longitudinal preparations. Conclusions and inferences: Dopamine is able to modulate contractile activity of the human colon. In the circular muscle layer, DA induces mainly muscular contraction activating non-neural D1-like receptors, coupled to PLC/IP3 pathway. In the longitudinal muscle layer, DA induces muscular relaxation acting on non-neural D2-like receptors leading to the increase in K + conductance. K E Y W O R D S circular and longitudinal muscle, dopamine, dopaminergic receptors human colon, intestinal motility

Role of enteric dopaminergic neurons in regulating peristalsis of rat proximal colon

“…Consistent with previous studies, 7,8,10‐12 bath‐applied dopamine caused a sustained dilation of the proximal colon segments (Figure 4A‐C). Although the D 1 ‐like receptor antagonist SCH 23390 itself reduces the frequency of peristaltic contractions, dopamine failed to cause a further reduction upon the blockade of D 1 ‐like receptors (Figure 4E, H), indicating that exogenous dopamine functions predominantly through D 1 ‐like receptors to inhibit colonic peristalsis.…”

“…In colonic muscle strips, bath‐applied dopamine attenuates cholinergic nerve‐mediated contractions by stimulating nitrergic and purinergic pathways via D 1 ‐like receptor activation 10 . Exogenous dopamine also reduces the amplitude and frequency of spontaneous phasic contractions via the activation of D 1 ‐like receptors 7,8,10‐12 . In addition, exogenous dopamine could stimulate adrenoceptors in the gastrointestinal tract.…”

Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management

“…In fact, IBS patients show lower dopamine levels in plasma [ 51 ] and urine [ 161 ] compared to healthy controls. Dopamine mediates colonic peristalsis, activating muscle contraction through D1 receptors and inhibiting it by D2 receptors [ 167 ], being related to motility dysfunction. However, the administration of dopamine or its agonists enhances IBS symptoms in patients with comorbid restless legs syndrome [ 168 ].…”

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

“…In another set of experiments the human colon responses to cumulative concentrations of 5-HT (0.1 µM-1 mM) were examined in the absence or in the presence of methysergide (10 µM). The concentrations of the drugs used were determined from the literature [28][29][30][31].…”