Platelet‐activating factor synthesis by peritoneal mast cells and its inhibition by two quinoline‐based compounds

Hogaboam, Cory M.; Donigi-Gale, D.; Shoupe, T. Scott; Bissonnette, Élyse; Befus, A. Dean; Wallace, John L.

doi:10.1111/j.1476-5381.1992.tb14215.x

Cited by 31 publications

(12 citation statements)

References 20 publications

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“…Of particular interest is the recent finding that PF 5901 will also inhibit PAF synthesis in rodent mast cells (Hogaboam et al, 1992). In recent studies, LTC4, LTD4 and LTE4 have been shown to increase airway responsiveness to histamine in asthmatic but not normal subjects (Arm et al, 1988;O'Hickey et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

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

Herd

Donigi-Gale²,

Shoupe³

et al. 1992

British J Pharmacology

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1 Aerosol administration of platelet activating factor (PAF) (80pjgml' for 60min) to neonatally immunized rabbits caused bronchoconstriction which was far in excess of that produced by a comparable aerosol of bovine serum albumin (BSA) D4 antagonist, at a dose of 10 mg (direct intratracheal administration) significantly inhibited the airway resistance (RL) component of the bronchoconstriction induced by PAF in neonatallyimmunized rabbits. Doses of 10 mg, 3 mg and 1 mg PF 5901 (direct intratracheal administration) were sufficient to inhibit significantly the PAF-induced increase in airways responsiveness to inhaled histamine in immunized rabbits. PF 5901 however, failed to alter the pulmonary cell infiltration induced by PAF, as assessed by BAL. 5 We suggest from the results of the present study that PAF induces consistent and long-lasting increases in airways responsiveness to histamine in immunized rabbits, which is mediated, at least in part, by products of the 5-lipoxygenase metabolic pathway. Furthermore, the inability of PF5901 to inhibit the influx of inflammatory cells into the airway lumen following PAF challenge may suggest that bronchial hyperresponsiveness and cellular infiltration are not strictly associated events.

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Section: Discussionmentioning

confidence: 99%

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

Herd

Donigi-Gale²,

Shoupe³

et al. 1992

British J Pharmacology

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“…Vascular leaks have been shown to occur after treatment with histamine (2,25,26), leukotriene B4 and C4 (16) endothelin 3 (15), platelet-activating factor (PAF), and hydroxytrytomine (20). Plateletactivating factor and histamine are two products which are released when mesenteric mast cells degranulate (5,10). Thus, factors that stimulate degranulation of mast cells could lead to additional increases in microvascular permeability beyond those produced by the particular experimental pertubation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Environmental Stress on the Architecture and Permeability of the Rat Mesenteric Microvasculature

WILSON¹,

Baldwin²

1998

Microcirculation

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“…Platelet activating factor also has ulcerogenic effects and has been proposed to be important in gastric ulcerogenesis from necrotizing agents (Wallace 1990). The inter-relationships between the metabolism of arachidonate and platelet-activating factor (Carlini et al 1985;Hogaboam et al 1992) and the activation of their metabolism by calcium (O'Flaherty 1988) suggests there are important interactions amongst all three of these mediators of potential importance in ulcerogenesis. Calcium antagonists have been shown to prevent ethanol-and indomethacin-induced gastric lesions in normal rats (Ghanayem et al 1987).…”

mentioning

confidence: 99%

Inhibition by Leukotriene Inhibitors, and Calcium and Platelet-activating Factor Antagonists, of Acute Gastric and Intestinal Damage in Arthritic Rats and in Cholinomimetic-treated Mice

1999

Journal of Pharmacy and Pharmacology

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The leukotrienes, platelet activating factor and intracellular calcium have been implicated in the development of gastro-intestinal lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs) but the relative significance of these inflammatory mediators in lesion formation has not been established in sensitive and specific models of gastro-intestinal ulceration. In the present study the effects of drugs affecting 5-lipoxygenase activity, the actions of platelet activating factor and intracellular calcium on the development of gastric and intestinal ulceration induced by NSAIDs were investigated in highly sensitive models of ulcerogenicity induced by treatment with either the cholinomimetic, acetyl-beta-methyl choline chloride, in mice (gastric mucosal lesions) or adjuvant-induced polyarthritis in rats (gastric and intestinal mucosal lesions) as well as in normal mice (intestinal mucosal lesions). The 5-lipoxygenase inhibitors, such as MK-886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-+ ++dimethylpropanoic acid), given at doses shown to reduce the indomethacin-induced increase in mucosal leukotriene B4 concentrations were found to partially prevent the development of gastric and intestinal lesion induced by indomethacin and gastric lesions from aspirin, but the same doses of MK-886 did not affect gastric lesions from diclofenac. Pretreatment with these inhibitors at both 3-5 h and 0-0.25 h was required to achieve protection against gastric mucosal damage from indomethacin. Immediate prior administration of platelet activating factor antagonists (e.g. WEB-2086) with the 5-lipoxygenase inhibitors did not affect gastric or intestinal lesions induced by indomethacin. The calcium antagonist, verapamil, was slightly protective against gastric and intestinal lesions induced by indomethacin. Gastric lesions were further prevented by combinations of a single dose of verapamil with a platelet activating factor antagonist but not combined with a 5-lipoxygenase inhibitor; other combinations of verapamil with lipoxygenase inhibitors or platelet-activating factor antagonists being without inhibitory effects on gastric or intestinal lesions compared with the drugs alone. These results show that 5-lipoxygenase products and intracellular calcium play a major role in acute gastric and intestinal damage by the NSAIDs, but platelet-activating factor has little or no appreciable involvement.

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Platelet‐activating factor synthesis by peritoneal mast cells and its inhibition by two quinoline‐based compounds

Cited by 31 publications

References 20 publications

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

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

Effects of Environmental Stress on the Architecture and Permeability of the Rat Mesenteric Microvasculature

Inhibition by Leukotriene Inhibitors, and Calcium and Platelet-activating Factor Antagonists, of Acute Gastric and Intestinal Damage in Arthritic Rats and in Cholinomimetic-treated Mice

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