Pathophysiologic Role of Neurotransmitters in Digestive Diseases

Abstract

Neurotransmitters are special molecules that serve as messengers in chemical synapses between neurons, cells, or receptors, including catecholamines, serotonin, dopamine, and other neurotransmitters, which play an important role in both human physiology and pathology. Compelling evidence has indicated that neurotransmitters have an important physiological role in various digestive diseases. They act as ligands in combination with central or peripheral receptors, and transmits signals through chemical synapses, which are involved in regulating the physiological and pathological processes of the digestive tract organs. For instance, neurotransmitters regulate blood circulation and affect intestinal movement, nutrient absorption, the gastrointestinal innate immune system, and the microbiome. In this review, we will focus on the role of neurotransmitters in the pathogenesis of digestive tract diseases to provide novel therapeutic targets for new drug development in digestive diseases.

Keywords: dopamine; gastrointestinal inflammation; liver fibrosis; neurotransmitters; serotonin.

FIGURE 1

The bidirectional neuroimmune interactions of 5-HT in the regulation and consequences of intestinal inflammation. Evidence from clinical and animal studies indicate that EC cells of the gastrointestinal (GI) tract are the main source of mucosal 5-HT, which acts a pro-inflammatory mediator by regulating immune cell activation leading to increased pro-inflammatory cytokine, such as TNF-α, IL-13, IL-6 (right side). However, 5-HT also can act on 5-HT receptors on goblet cells to increase mucus secretion, and decrease IL-10, INF-γ through regulating 5-HT receptors on immune cell (left side).

FIGURE 2

Schematic representation summarizes the DRD2 and ADRB2 signaling in digestive disease. Activated ADRB2 induced pancreatic cancer cell invasion by accumulation of cAMP, promoted gastric cancer proliferation and anti-apoptosis through inducing autophagy. Also, it promoted gastric cancer progression metastasis, angiogenesis via VEGFR-2. The DRD2 signaling activates PP2A and inhibited the phosphorylation of Akt and NF-kappa B to control inflammation, However, it promoted pancreatic cancer, the underlying mechanism is unknown. Besides, it inhibits tumor angiogenesis by inhibiting VEGFR-2 phosphorylation in gastric cancer endothelial cells. DRD2 activation suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway. Moreover, it downregulated VEGFR1, p-ERK and pJNK to ameliorate liver cancer progression.