The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis.
This study evaluated the effects of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA), in two murine models of colitis, the dextran sodium sulphate-induced colitis and the spontaneous colitis found in interleukin-10 gene deficient mice. IB-MECA was given orally twice a day at a dose of either 1 or 3 mg/kg/day. Evaluation of colon damage and inflammation was determined grossly (body weight, rectal bleeding) and biochemically (colon levels of myeloperoxidase, malondialdehyde, chemokines and cytokines). There was significantly increased inflammatory cell infiltration into the colon associated with an increase in colon levels of cytokines and chemokines; with subsequent free radical related damage in both dextran sodium sulphate-induced colitis and 10-week-old interleukin-10(-/-) mice. IB-MECA protected in both models against the colitis induced inflammatory cell infiltration and damage and attenuated the increases in colon inflammatory cytokine and chemokine levels. Thus activation of the adenosine A(3) receptor is effective in protecting against colitis.
Mabley
Jon
J
Inotek Pharmaceuticals Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA. jmabley@inotekcorp.com
Soriano
Francisco
F
Pacher
Pál
P
Haskó
György
G
Marton
Anita
A
Wallace
Rebecca
R
Salzman
Andrew
A
Szabó
Csaba
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D012002:Rectal Diseases / Q000517:prevention & control; D015431:Weight Loss / Q000187:drug effects
D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D018664:Interleukin-12; D008315:Malondialdehyde; D016264:Dextran Sulfate; D009195:Peroxidase; D000241:Adenosine