Effect of a 5-lipoxygenase inhibitor and leukotriene antagonist (PF 5901) on antigen-induced airway responses in neonatally immunized rabbits.

1. The effect of a single intratracheal dose (10 mg) of PF 5901 (2-[3(1-hydroxyhexyl) phenoxymethyl] quinoline hydrochloride, a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism and a leukotriene D4 antagonist) on airway changes induced in response to Alternaria tenuis aerosol challenge was assessed in adult rabbits neonatally immunized. Leukotriene generation was determined in vivo by measuring leukotriene B4 (LTB4) levels in bronchoalveolar lavage (BAL) fluid and ex vivo by measuring calcium ionophore-stimulated production of LTB4 in whole blood.

Effect of PF 10040 on PAF-induced airway responses in neonatally immunized rabbits.

1. PF 10040 displaced [3H]-PAF from binding sites on rabbit platelets with an IC50 = 1.07 x 10(-5) M, which was approximately three orders of magnitude below that of a standard PAF antagonist WEB 2086 (IC50 = 4.

Protective effects of PF-10040 in experimental NSAID-gastritis: role of leukocytes, leukotrienes and PAF.

The effects and mechanism of action of PF-10040, a quinoline derivative, were examined in an experimental model of NSAID-gastritis. Oral pretreatment with PF-10040 dose-dependently reduced the severity of indomethacin-induced gastric damage, with a significant protective effect being observed with doses of 10 mg/kg or greater. The protective effects of this compound persisted for as long as 6 h after administration.

Effect of a 5-lipoxygenase inhibitor and leukotriene antagonist (PF 5901) on PAF-induced airway responses in neonatally immunized rabbits.

1. Aerosol administration of platelet activating factor (PAF) (80 micrograms ml-1 for 60 min) to neonatally immunized rabbits caused bronchoconstriction which was far in excess of that produced by a comparable aerosol of bovine serum albumin (BSA), the carrier molecule for PAF. Bronchoconstriction of a similar magnitude was elicited by PAF in immunized, sham-immunized and normal rabbits.

The role of complement, platelet-activating factor and leukotriene B4 in a reversed passive Arthus reaction.

1. The mechanisms underlying oedema formation induced in a reversed passive Arthus (RPA) reaction and, for comparison, in response to zymosan in rabbit skin were investigated. 2.