Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice.
In this study, the involvement of 5-HT2A receptors on mesenteric ischemia-reperfusion injury was examined in mice. Intestinal ischemia produced by 45 min occlusion of superior mesenteric artery was followed by 24h reperfusion (I/R). The 5-HT2A selective antagonist, ketanserin (0.5 mgkg(-1)) or the 5-HT2A agonist DOI (0.25 mgkg(-1)) was intravenously administered before ischemia and 8h after the beginning of reperfusion. The effects were compared with those obtained in sham operated animals (S). Ketanserin prevented the upper gastrointestinal transit delay induced by I/R (P<0.01), protected intestine from leukocyte recruitment as indicated by jejunal myeloperoxidase activity (P<0.05) and reverted Evans Blue extravasation elicited by I/R in lung, colon and jejunum (P<0.05). On the other hand, 5-HT2A activation by DOI mimicked the effects of I/R in S mice prolonging small intestine transit (P<0.05) and enhancing neutrophil accumulation in jejunal tissues (P<0.05). Furthermore, the reduction of ADP-induced platelet aggregation in plasma of I/R mice was prevented by ketanserin treatment. All together, these findings support the critical involvement of 5-HT2A receptor subtype in mediating the damage induced by mesenteric I/R in mice.
Bertoni
Simona
S
Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, Viale G.P. Usberti 27/A, 43100 Parma, Italy.
Ghizzardi
Paola
P
Cattaruzza
Fiore
F
Ballabeni
Vigilio
V
Impicciatore
Mariannina
M
Tognolini
Massimiliano
M
Lagrasta
Costanza A M
CA
Barocelli
Elisabetta
E
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D007650:Ketanserin; D009195:Peroxidase; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine