Differential antagonism of platelet activating factor-induced neutrophilia and gastric hemorrhage in the rat.
Intravenous injection of platelet activating factor (PAF) in rats produced hypotension, neutrophilia, gastric congestion, and sloughing of the gastric epithelium. The congestion was quantified by measuring hemoglobin in the gastric mucosa. Other lesions were quantified by scores of gross pathology and histopathology. PAF-induced changes in neutrophil levels were prevented by pretreatment with the PAF-antagonist Ro24-4736, but not by the PAF-antagonist CV-3988. Both PAF antagonists reduced the hypotension, the amount of hemoglobin in the gastric mucosa, and the PAF-induced gastric pathology. These results suggest that PAF receptors involved in PAF-induced neutrophil mobilization respond differently from PAF receptors in the gastrointestinal and cardiovascular systems.
Thomas
T K
TK
Department of Pharmacology, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Chesonis
R S
RS
Schmolze
D
D
Symington
J
J
Harbison
M L
ML
Walser
A
A
Will
P C
PC
D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000188:drug therapy; D006454:Hemoglobins / Q000378:metabolism; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy; D007275:Injections, Intravenous; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D010617:Phenanthridines / Q000494:pharmacology*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*
D006454:Hemoglobins; D010617:Phenanthridines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D014227:Triazines; C071318:Ro 24-4736; C037913:CV 3988