Platelet activating factor as a proinflammatory mediator in acetic-induced colitis in the rat.
Platelet activating factor (PAF) induces neutrophilia and produces a variety of gastrointestinal lesions. The role of PAF as a proinflammatory mediator was examined by measuring the production of PAF and the efficacy of the PAF antagonists WEB 2086 and Ro 24-0238 in acetic acid (HOAc)-induced colitis. PAF levels within the colonic mucosa, as measured by radioimmunoassay, increased from 259 +/- 119 ng/mg in control tissue, to 616 +/- 266 ng/mg in HOAc inflamed tissue. The accumulation of neutrophils within the mucosa was decreased by 53 +/- 10% by pretreatment with 3 mg/kg WEB 2086, and by 43 +/- 11% by 3 mg/kg Ro 24-0238. PAF-induced neutrophilia had no effect on the severity of HOAc-induced colitis, therefore, PAF my be involved in sustaining the chronic inflammation of colitis.
Will
P C
PC
Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Thomas
T K
TK
Iverson
L
L
Buckman
D
D
Weis
W
W
Wilson
C
C
Srivastava
A
A
D000085:Acetates; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D053284:Polyunsaturated Alkamides; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology
D000085:Acetates; D001381:Azepines; D010972:Platelet Activating Factor; D053284:Polyunsaturated Alkamides; D011725:Pyridines; D014230:Triazoles; C052518:WEB 2086; C073133:Ro 24-0238