Vasopressin augments TNBS‐induced colitis through enteric neuronal V_1a receptor‐mediated COX‐2‐dependent prostaglandin release from mast cells in mice

Abstract

Background Inflammatory bowel disease (IBD) is a functional disorder with chronic and relapsing clinical features. Vasopressin (VP) is a hormone responsible for water and stress homeostasis and also regulates gastrointestinal inflammation and motility. We explored whether VP was related to IBD pathogenesis and its possible pathway. Methods Colitis was induced by 2,4,6‐trinitrobenzenesulfonic acid (TNBS) in mice. The disease activity and colonic damage were evaluated through a scoring system. Locations of the V1a receptor were revealed by immunochemistry method in colon. Ussing chamber technique was performed for the electrophysiological characterization by using rat ileum. The (Arg8)‐Vasopressin (AVP)‐evoked short‐circuit current (Isc) was recorded in the presence of conivaptan (V1a and V2 receptor antagonist), tolvaptan (V1b receptor antagonist), tetrodotoxin (TTX), atropine, cyclooxygenase (COX) inhibitors (indomethacin, nonspecific COX antagonist; SC560, COX‐1 antagonist; NS560, COX‐2 antagonist), and a stabilizer of mast cell (cromolyn sodium), respectively. Key Results TNBS resulted in the obvious loss of body weight and tissue damages in mice. AVP significantly aggravated the TNBS‐induced colitis, which was attenuated by conivaptan but not tolvaptan. V1a receptors were found immunopositive in neurons among the enteric nervous system. AVP evoked a pulsatile response in Isc. Its amplitude, frequency, and cycle duration were around 8‐15 µA/cm2, 10‐11 mHz, and 1.5 minutes, respectively. Notably, the AVP‐evoked change in Isc was abolished by TTX, atropine, conivaptan, indomethacin, NS560, and cromolyn sodium, respectively. Conclusions and Inferences VP‐V1a receptor played the proinflammatory role in TNBS‐induced colitis by promoting COX‐2‐dependent prostaglandin release from mucosal mast cells, which was mediated by the cholinergic pathway.

Synergistic augmentation of rhythmic myogenic contractions of human stomach by arginine vasopressin and adrenaline: Implications for the induction of nausea

“…Low concentrations of AVP caused muscle contraction and stimulated myogenic contractions. This was independent of neuronal activity or mast cell functions (stimulated by AVP activating enteric neurons in mice with 2,4,6‐trinitrobenzenesulfonic acid [TNBS]‐induced colitis; Dou et al, 2019 ), and AVP did not modulate cholinergically mediated contractions. In proximal stomach, the AVP‐induced increase in tone was maintained and appeared unrelated to increases in spontaneous contractions.…”

Luteolin, a Potent Human Monoamine Oxidase-A Inhibitor and Dopamine D4 and Vasopressin V1A Receptor Antagonist

“…Similarly, the peripheral role of V 1A R in the inflammatory process of inflammatory bowel disease (IBD) mediated by prostaglandin release was recently reported . In that report, V 1A R was shown to promote COX-2-dependent prostaglandin release from mucosal mast cells in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, which was attenuated by conivaptan (a V 1A R antagonist).…”

“…58 Similarly, the peripheral role of V 1A R in the inflammatory process of inflammatory bowel disease (IBD) mediated by prostaglandin release was recently reported. 59 In that report, V 1A R was shown to promote COX-2-dependent prostaglandin release from mucosal mast cells in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice, which was attenuated by conivaptan (a V 1A R antagonist). Additionally, impaired renal water excretion, abnormal renal hemodynamics, and high AVP levels in a mouse model of CCl 4 -induced liver cirrhosis have been reported by Linas et al 60 Similarly, a recent study found upregulated V 1 R expression in the hepatocytes of an ischemia−reperfusion injury mouse model and highlighted the importance of the hepatocyte V 1 R/Wnt/β-catenin/ FoxO3a/Akt pathway in hepatoprotection.…”

Crosstalk between omega-6 oxylipins and the enteric nervous system: Implications for gut disorders?

“…Treatment of myenteric ganglia from the guinea pig colon or ileum with PGE 2 led to prolonged depolarization of enteric neurons with enhanced spike discharge together with an increased neuronal excitability ( 39 – 41 ) ( Figure 2 ). More recently, myenteric neuron activity and contraction have been shown to depend on prostaglandin release (COX-2 pathway) from mucosal mast cells in a model of TNBS-induced colitis ( 42 ). Similar findings were observed when submucosal neurons of guinea pig colon were treated with PGD 2 ( 43 ).…”