ATROPINE INHIBITS THROMBOXANE A2 GENERATION IN ISOLATED LUNGS OF THE GUINEA‐PIG

Abstract

1 Histamine (0.5 to 5 μg) and slow reacting substance of anaphylaxis (SRS-A, 0.05 to 0.3 u), injected in the isolated, perfused lungs of normal and ovalbumin-sensitized guinea-pigs, promote formation and release of thromboxane A₂(TXA₂) and other arachidonate metabolites, the effect being more pronounced in sensitized lungs. 2 Carbachol injected (1 to 10 μg) or perfused (1 μg ml⁻¹ min⁻¹) through normal or sensitized lungs does not elicit formation of TXA₂ and prostaglandins. Furthermore the increased generation of arachidonate metabolites due to histamine is not altered by carbachol. 3 Atropine and ipratropium bromide (1 μg ml⁻¹ min⁻¹) reduce significantly the increased rate of production of TXA₂ caused by histamine and SRS-A both in normal and sensitized lungs, whereas hexamethonium (10 to 25 μg ml⁻¹ min⁻¹) is ineffective. 4 The mechanism of action of atropine in inhibiting the increased generation of TXA₂ is clearly not related to its antimuscarinic or antihistaminic properties. The drug might act at the early events, involved in the activation of arachidonic acid metabolism. The results suggest new sites of action for atropine which, besides the control of the vagal bronchomotor tone, interferes directly with the primary mediators of anaphylaxis.