Platelet-activating factor induces nonspecific desensitization to bronchodilators in guinea pigs

Devendra K. Agrawal, D. R. Bergren, P. J. Byorth, R. G. Townley

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Abstract

Platelet-activating factor (PAF) is a potent mediator of inflammation and is a mediator which is known to cause airway hyperresponsiveness in human and experimental animals. However, the mechanism of action of PAF is not clear. In this study we examined the effect of methacholine upon specific airway resistance (SRaw) in guinea pigs and the ability of either isoproterenol or prostaglandin E2 to reverse this effect both before and after PAF administration at sub-bronchoactive doses in conscious guinea pigs as well as in isolated airway tissues. SRaw in conscious guinea pigs was monitored using a whole-body plethysmograph. In nonsensitized guinea pigs, a concentration of PAF (0.1 μg/ml), which by itself did not affect SRaw, potentiated the methacholine-induced increase in SRaw. In ovalbumin-sensitized animals, the response to methacholine was significantly greater as compared to the nonsensitized group. Prior administration of PAF did not potentiate the response to methacholine in ovalbumin-sensitized animals. In isolated tracheal rings and lung parenchymal strips of nonsensitized guinea pigs, preincubation of the tissue with 0.1 μM PAF decreased the sensitivity of isoproterenol to induce relaxation. However, in the ovalbumin-sensitized group of guinea pig tracheas or lung parenchymas, PAF did not reduce further the effect of isoproterenol to elicit relaxation. Furthermore, PAF did not alter the affinity or the density of beta adrenoceptors in guinea pig lung membranes. These data suggest that PAF may potentiate the responses to bronchoconstrictors and desensitize the responses to bronchodilators in a nonspecific manner. This may be a mechanism underlying PAF-induced airway hyperresponsiveness in asthma.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume259
Issue number1
StatePublished - 1991

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Platelet Activating Factor
Bronchodilator Agents
Guinea Pigs
Methacholine Chloride
Ovalbumin
Isoproterenol
Lung
Bronchoconstrictor Agents
Inflammation Mediators
Airway Resistance
Trachea
Dinoprostone
Adrenergic Receptors
Asthma
Membranes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Platelet-activating factor induces nonspecific desensitization to bronchodilators in guinea pigs. / Agrawal, Devendra K.; Bergren, D. R.; Byorth, P. J.; Townley, R. G.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 259, No. 1, 1991, p. 1-7.

Research output: Contribution to journalArticle

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