PMID: 8996198Jan 1, 1997Paper

The influence of endogenous catecholamines on the inhibitory effects of rolipram against early- and late-phase response to antigen in the guinea pig

The Journal of Pharmacology and Experimental Therapeutics
D C UnderwoodT J Torphy

Abstract

Selective inhibitors of the low-Km cAMP-specific phosphodiesterase (PDE4) inhibit inflammatory cell function and relax airway smooth muscle. Thus PDE4 inhibitors may be useful in the therapy of asthma. The present study was conducted to determine whether the in vivo activity of rolipram, a prototypical PDE4 inhibitor, is due to its ability to potentiate the anti-inflammatory effects of prostaglandins or catecholamines, endogenous activators of adenylyl cyclase, in models of the early- and late-phase response to antigen. Rolipram, administered i.v. to anesthetized, paralyzed and ventilated ovalbumin-sensitized guinea pigs, inhibited i.v. antigen-induced bronchoconstriction with an ID50 value of 0.2 mg/kg. Pretreatment with either of the beta adrenoceptor antagonists propranolol and nadolol (0.5 mg/kg i.v.), enhanced the bronchial reactivity to antigen and abolished the inhibitory activity of rolipram (0.1-10 mg/kg i.v.). In addition, the inhibitory activity of three structurally dissimilar PDE4 inhibitors was nearly abolished by propranolol. Cyclooxygenase inhibition by indomethacin slightly enhanced the reactivity to antigen but did not affect the inhibitory activity of rolipram. Plasma catecholamine concentrations were not alt...Continue Reading

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