Rasagiline, an inhibitor of <scp>MAO</scp>‐B, decreases colonic motility through elevating colonic dopamine content

Liu, Caixia; Zhang, X.‐L.; Zhou, Li; Wang, T.; Quan, Zhusheng; Zhang, Y.; Li, J.; Li, G.‐W.; Zheng, Li‐Fei; Li, L.‐S.; Zhu, Jin-Xia

doi:10.1111/nmo.13390

Cited by 17 publications

(13 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In DAT knockout mice or rats treated with rasagiline, an inhibitor of the main dopamine‐degrading enzyme monoamine oxidase‐B, the resultant increases in tissue concentration of dopamine is associated with attenuation of colonic motility 24,28 . In the present study, an acute increase in the synaptic dopamine level with the DAT inhibitor GBR 12909 caused a reduction in the frequency of propagating peristaltic waves (Figure 3I, J), suggesting that excessive “synaptic” dopamine inhibits colonic peristalsis (Figure S2C).…”

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

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

Nakamori

Noda

Mitsui

et al. 2021

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Constipation is commonly seen in patients with Parkinson's disease associated with a loss of dopaminergic neurons in both central and enteric nervous systems. However, the roles of enteric dopaminergic neurons in developing constipation remain to be elucidated. Here, we investigated the roles of enteric dopaminergic neurons in the generation of colonic peristalsis. Methods Cannulated segments of rat proximal colon were situated in the organ bath, abluminally perfused with physiological salt solution and luminally perfused with 0.9% saline. Drugs were applied in the abluminal solution. Changes in diameter along the length of the colonic segment were captured by a video camera and transformed into spatio‐temporal maps. Fluorescence immunohistochemistry was also carried out. Key Results Blockade of nitrergic neurotransmission prevented oro‐aboral propagation of peristaltic waves and caused a colonic constriction without affecting ripples, non‐propagating myogenic contractions. Blockade of cholinergic neurotransmission also prevented peristaltic waves but suppressed ripples with a colonic dilatation. Tetrodotoxin (0.6 μM) abolished peristaltic waves and increased ripples with a constriction. SCH 23390 (20 μM), a D1‐like dopamine receptor antagonist, slowed the peristaltic waves and caused a constriction, while GBR 12909 (1 μM), a dopamine reuptake inhibitor, diminished the peristaltic waves with a dilatation. Bath‐applied dopamine (3 μM) abolished the peristaltic waves associated with a colonic dilation in an SCH 23390 (5 μM)‐sensitive manner. D1 receptor immunoreactivity was co‐localized to nitrergic and cholinergic neurons. Conclusions and Inferences Dopaminergic neurons appear to facilitate nitrergic neurons via D1‐like receptors to stabilize asynchronous contractile activity resulting in the generation of colonic peristalsis.

show abstract

Section: Discussionsupporting

confidence: 54%

“…In colonic muscle strips, the D 1 ‐like receptor antagonist SCH 23390 increases the frequency and amplitude of spontaneous phasic contractions, 7,8,10,23,24 and also enhanced cholinergic nerve‐mediated contractions 10 . Thus, it was envisaged that D 1 ‐like receptor blockade exhibits prokinetic effect on peristaltic waves.…”

Section: Discussionmentioning

confidence: 99%

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

Nakamori

Noda

Mitsui

et al. 2021

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

“…This coumarin, C18 or 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2 h-chromen-2-one, is an inhibitor of monoamine oxidase-B, which is abundant in the muscular layers of the rats' colon. Its administration increases dopamine which inhibits colon motility 26 , which suggest mobility of the colon in DCS. This deserves to be confirmed.…”

Section: Expression Of Metabolites Indicating An Alteration Of the Homentioning

confidence: 99%

Cecal metabolome fingerprint in a rat model of decompression sickness with neurological disorders

Maistre¹,

Gaillard²,

Martin³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Massive bubble formation after diving can lead to decompression sickness (DCS), which can result in neurological disorders. We demonstrated that hydrogen production from intestinal fermentation could exacerbate DCS in rats fed with a standard diet. The aim of this study is to identify a fecal metabolomic signature that may result from the effects of a provocative hyperbaric exposure. The fecal metabolome was studied in two groups of rats previously fed with maize or soy in order to account for diet effects. 64 animals, weighing 379.0_20.2 g on the day of the dive, were exposed to the hyperbaric protocol. The rats were separated into two groups: 32 fed with maize (Div MAIZE) and 32 fed with soy (Div SOY). Gut fermentation before the dive was estimated by measuring exhaled hydrogen. Following hyperbaric exposure, we assessed for signs of DCS. Blood was analyzed to assay inflammatory cytokines. Conventional and ChemRICH approaches helped the metabolomic interpretation of the cecal content. The effect of the diet is very marked at the metabolomic level, a little less in the blood tests, without this appearing strictly in the clinic status. Nevertheless, 37 of the 184 metabolites analyzed are linked to clinical status. 35 over-expressed compounds let suggest less intestinal absorption, possibly accompanied by an alteration of the gut microbial community, in DCS. The decrease in another metabolite suggests hepatic impairment. This spectral difference of the ceca metabolomes deserves to be studied in order to check if it corresponds to functional microbial particularities.

show abstract

“…In our study, β-PEA and Klamin ® were applied directly on the intestinal muscle strips, so their activity was similar. However, if considering oral intake, pure β-PEA would rapidly be degraded by selective MAO-B enzymes, highly expressed in muscular layer and myenteric plexus of human colon [47]. On the contrary, Klamin ® , besides its natural β-PEA content, also contains molecules, such as AFA-phycocyanins, Mycosporine-like aminoacids (MAAs), and phycochrome, that have shown to be the most powerful natural selective MAO-B enzymes inhibitors [36].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

show abstract

Rasagiline, an inhibitor of MAO‐B, decreases colonic motility through elevating colonic dopamine content

Cited by 17 publications

References 44 publications

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

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

Cecal metabolome fingerprint in a rat model of decompression sickness with neurological disorders

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

Contact Info

Product

Resources

About