The protective effect of α7-nACh receptor and its interaction with 5-HT1B/1D receptors in acute intestinal ischemia-reperfusion injury in rats

Over the past decades, great attention has been given to the nervous system modulating effects on the immune response in inflammation-associated injuries, such as acute intestinal ischemia-reperfusion (IR). Recently, we proved the anti-inflammatory and antioxidant effects of 5-hydroxytryptamine (5-HT)1B/1D receptors in intestinal IR injury in rats. Also, the alpha7 nicotinic acetylcholine (alpha 7-nACh) receptor has anti-inflammatory effects in different inflammation-associated injuries. Starting from these premises, we aimed to examine the function of the alpha 7-nACh receptors and the functional interactions between the anti-inflammatory and antioxidant effects of alpha 7-nACh and 5-HT1B/1D receptors in acute intestinal IR injury. To confirm the expression and localization of alpha 7-nACh receptors on the ileum nerves, an immunofluorescence-based method was applied. Then, intestinal IR injury was induced by 30-min occlusion of superior mesenteric artery and reperfusion for 2 h in rats. Acute systemic administration of alpha 7-nACh receptor agonist PNU-282987 and antagonist methyllycaconitine, and 5-HT1B/1D receptors agonist (sumatriptan) and antagonist (GR127, 935) were used in the model of intestinal IR injury. Finally, biochemical and histological parameters were assessed. Alpha 7-nACh receptors were expressed by 9% on the ileum nerves. Likewise, activation of the alpha 7-nACh receptor showed anti-inflammatory and antioxidant effects in intestinal IR injury but not as well as 5-HT1B/1D receptors. Interestingly, 5-HT1B/1D receptors via attenuation of glutamate (Glu) release indirectly activated the alpha 7-nACh receptor and its protective effects against inflammation and oxidative stress. The protective effect of the alpha 7-nACh receptor on intestinal IR injury was activated indirectly through the 5-HT1B/1D receptors' modulatory impact on Glu release.