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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 H2, 3 ; Mohammad Jafari R3 ; Abdollahi A4 ; Pasalar P1 ; Dehpour AR2, 3, 5
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Imam Hospital Complex, Tehran, Iran
  5. 5. Brain and Spinal Injury Repair Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

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
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Ahmad Reza Dehpour (5)
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