The Protective Effect of Α7-Nach Receptor and Its Interaction With 5-Ht1b/1D Receptors in Acute Intestinal Ischemia-Reperfusion Injury in Rats Publisher Pubmed



Gharishvandi F¹ ; Shafaroodi H^{2, 3} ; Mohammad Jafari R³ ; Abdollahi A⁴ ; Pasalar P¹ ; Dehpour AR^{2, 3, 5}
Source: Fundamental and Clinical Pharmacology Published:2022

Abstract

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 (α7-nACh) receptor has anti-inflammatory effects in different inflammation-associated injuries. Starting from these premises, we aimed to examine the function of the α7-nACh receptors and the functional interactions between the anti-inflammatory and antioxidant effects of α7-nACh and 5-HT1B/1D receptors in acute intestinal IR injury. To confirm the expression and localization of α7-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 α7-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. Α7-nACh receptors were expressed by 9% on the ileum nerves. Likewise, activation of the α7-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 α7-nACh receptor and its protective effects against inflammation and oxidative stress. The protective effect of the α7-nACh receptor on intestinal IR injury was activated indirectly through the 5-HT1B/1D receptors’ modulatory impact on Glu release. © 2021 Societe Francaise de Pharmacologie et de Therapeutique