Dopamine Receptors in the Gastrointestinal Tract

Zhang, Xiaoli; Liu, Sumei; Sun, Qi; Zhu, Jin-Xia

doi:10.1007/978-981-33-6586-5_3

Cited by 4 publications

(2 citation statements)

References 78 publications

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“…ARI is partial agonist of dopamine D2 receptors [ 43 ], while TRZ works through plethora of receptors and transporters (serotonin, histamine, adrenalin/noradrenalin) [ 44 ]. Nevertheless, many of these receptors are found at the periphery [ 45 , 46 ], and we cannot fully exclude the possibility that the sterol biosynthesis inhibiting effects arise by this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effects of Psychotropic Medication on Somatic Sterol Biosynthesis of Adult Mice

et al. 2022

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Polypharmacy is commonly used to treat psychiatric disorders. These combinations often include drugs with sterol biosynthesis inhibiting side effects, including the antipsychotic aripiprazole (ARI), and antidepressant trazodone (TRZ). As the effects of psychotropic medications are poorly understood across the various tissue types to date, we investigated the effects of ARI, TRZ, and ARI + TRZ polypharmacy on the post-lanosterol biosynthesis in three cell lines (Neuro2a, HepG2, and human dermal fibroblasts) and seven peripheral tissues of an adult mouse model. We found that both ARI and TRZ strongly interfere with the function of 7-dehydrocholesterol reductase enzyme (DHCR7) and lead to robust elevation in 7-dehydrocholesterol levels (7-DHC) and reduction in desmosterol (DES) across all cell lines and somatic tissues. ARI + TRZ co-administration resulted in summative or synergistic effects across the utilized in vitro and in vivo models. These findings suggest that at least some of the side effects of ARI and TRZ are not receptor mediated but arise from inhibiting DHCR7 enzyme activity. We propose that interference with sterol biosynthesis, particularly in the case of simultaneous utilization of medications with such side effects, can potentially interfere with functioning or development of multiple organ systems, warranting further investigation.

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Section: Discussionmentioning

confidence: 99%

Effects of Psychotropic Medication on Somatic Sterol Biosynthesis of Adult Mice

et al. 2022

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“…The identified association suggests possible participation of TAAR9 in gut dopamine signaling, although it cannot explain the mechanism of this participation. It is well established that dopamine in the digestive tract is essential for secretion and absorption, mucosal homeostasis, regeneration, and protection [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

et al. 2022

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Trace amine-associated receptors (TAAR1-TAAR9) are a family of G-protein-coupled monoaminergic receptors which might have great pharmacological potential. It has now been well established that TAAR1 plays an important role in the central nervous system. Interestingly, deletion of TAAR9 in rats leads to alterations in the periphery. Previously, we found that knockout of TAAR9 in rats (TAAR9-KO rats) decreased low-density lipoprotein cholesterol levels in the blood. TAAR9 was also identified in intestinal tissues, and it is known that it responds to polyamines. To elucidate the role of TAAR9 in the intestinal epithelium, we analyzed TAAR9-co-expressed gene clusters in public data for cecum samples. As identified by gene ontology enrichment analysis, in the intestine, TAAR9 is co-expressed with genes involved in intestinal mucosa homeostasis and function, including cell organization, differentiation, and death. Additionally, TAAR9 was co-expressed with genes implicated in dopamine signaling, which may suggest a role for this receptor in the regulation of peripheral dopaminergic transmission. To further investigate how TAAR9 might be involved in colonic mucosal homeostasis, we analyzed the fecal microbiome composition in TAAR9-KO rats and their wild-type littermates. We identified a significant difference in the number of observed taxa between the microbiome of TAAR9-KO and wild-type rats. In TAAR9-KO rats, the gut microbial community became more variable compared with the wild-type rats. Furthermore, it was found that the family Saccharimonadaceae, which is one of the top 10 most abundant families in TAAR9-KO rat feces, is almost completely absent in wild-type animal fecal samples. Taken together, these data indicate a role of TAAR9 in intestinal function.

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Dopamine in the regulation of glucose and lipid metabolism: a narrative review

Li,

Zheng,

Wang

et al. 2024

Obesity

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ObjectiveOwing to the global obesity epidemic, understanding the regulatory mechanisms of glucose and lipid metabolism has become increasingly important. The dopaminergic system, including dopamine, dopamine receptors, dopamine transporters, and other components, is involved in numerous physiological and pathological processes. However, the mechanism of action of the dopaminergic system in glucose and lipid metabolism is poorly understood. In this review, we examine the role of the dopaminergic system in glucose and lipid metabolism.ResultsThe dopaminergic system regulates glucose and lipid metabolism through several mechanisms. It regulates various activities at the central level, including appetite control and decision‐making, which contribute to regulating body weight and energy metabolism. In the pituitary gland, dopamine inhibits prolactin production and promotes insulin secretion through dopamine receptor 2. Furthermore, it can influence various physiological components in the peripheral system, such as pancreatic β cells, glucagon‐like peptide‐1, adipocytes, hepatocytes, and muscle, by regulating insulin and glucagon secretion, glucose uptake and use, and fatty acid metabolism.ConclusionsThe role of dopamine in regulating glucose and lipid metabolism has significant implications for the physiology and pathogenesis of disease. The potential therapeutic value of dopamine lies in its effects on metabolic disorders.

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Dopamine Receptors in the Gastrointestinal Tract

Cited by 4 publications

References 78 publications

Effects of Psychotropic Medication on Somatic Sterol Biosynthesis of Adult Mice

Effects of Psychotropic Medication on Somatic Sterol Biosynthesis of Adult Mice

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

Dopamine in the regulation of glucose and lipid metabolism: a narrative review

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