Intestinal ischemia-reperfusion injury alters purinergic receptor expression in clinically relevant extraintestinal organs.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Milano
Peter M
PM
Department of Surgery, Division of Trauma and Critical Care, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Douillet
Christelle D
CD
Riesenman
Paul J
PJ
Robinson
William P
WP
Beidler
Stephanie K
SK
Zarzaur
Ben L
BL
Rich
Preston B
PB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D007422:Intestines / Q000473:pathology / Q000502:physiology*; D007668:Kidney / Q000502:physiology; D008168:Lung / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D043704:Receptor, Adenosine A2B / Q000235:genetics; D043684:Receptor, Adenosine A3 / Q000235:genetics; D011983:Receptors, Purinergic / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C546469:P2rx7 protein, mouse; C546386:P2ry2 protein, mouse; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; D000255:Adenosine Triphosphate
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