Quinacrine prevention of intestinal ischaemic mucosal damage is partly mediated through inhibition of intraluminal phospholipase A2.
The influence of total ischaemia and revascularization on luminal phospholipid metabolism in the rat small intestine was investigated. Two hours of total ischaemia followed by five minutes of revascularization caused increases in phospholipase A2 activity, and lysophosphalidylcholine content in the gut lumen. The above treatment also resulted in mucosal damage expressed as an increase in N-acetyl-beta-glucosaminidase activity in the lumen. Pretreatment of animals with the phospholipase A2 inhibitor, quinacrine prevented the increases in luminal phospholipase A2 activity and mucosal damage following ischaemia and revascularization. Intraluminal injection of either phospholipase A2 purified from snake venom or Triton X-100 resulted in increased activity of N-acetyl-beta-glucosaminidase in the luminal content. Again, quinacrine pretreatment of animals prevented the increases in mucosal permeability and activity of N-acetyl-beta-glucosaminidase after intraluminal injection of purified phospholipase A2. On the other hand quinacrine pretreatment had no influence on the observed effects of Triton X-100 treatment. These findings suggest that an increase in luminal phospholipase A2 could be involved in mediating the mucosal injury caused by small intestinal ischaemia.
Otamiri
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T
Clinical Research Center, University of Linköping, Sweden.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D007082:Ileum / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000378:metabolism; D007511:Ischemia / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D010539:Permeability; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008244:Lysophosphatidylcholines; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000118:Acetylglucosaminidase; D011796:Quinacrine