Intestinal Ischemia-Reperfusion Injury Alters Purinergic Receptor Expression in Clinically Relevant Extraintestinal Organs

Abstract

Intestinal ischemia-reperfusion (IIR) injury is known to initiate the systemic inflammatory response syndrome, which often progresses to multiple organ failure. We investigated changes in purinoceptor expression in clinically relevant extra-intestinal organs following IIR injury. Anesthetized adult male BalbC mice were randomized to sham laparotomy (control, n = 5), or 15 min of superior mesenteric artery occlusion. Experimental ischemia was followed by a period of reperfusion [1 min (n = 6) or 1 h (n = 6)]. Mice were then sacrificed and lung, kidney, and intestinal tissues were harvested. Following RNA extraction, purinoceptor mRNA expression for P2Y2, A3, P2X7, A2b, P2Y4, and P2Y6 was analyzed using real-time RT-PCR. Significant differences in purinoceptor expression were observed in the lungs and kidneys of mice exposed to IIR injury when compared to controls. Pulmonary P2Y2 receptor expression was increased in the 1 h IIR group when compared to control, while pulmonary A3 receptor expression was incrementally elevated following IIR injury. In the kidney, P2Y2 receptor expression was increased in the 1 h IIR group compared to both 1 min IIR and control, and A3 receptor expression was decreased in the 1 h IIR group compared to the 1 min IIR group. No significant changes were observed in the intestinal purinoceptor profiles. Purinoceptor expression is altered in the murine lung and kidney, but not intestine following experimental IIR injury. These findings may implicate extracellular nucleotides and purinoceptors as possible mediators of the extra-intestinal organ dysfunction associated with IIR injury.