title: Atropine inhibits thromboxane A2 generation in isolated lungs of the guinea-pig.
abstract: 1 Histamine (0.5 to 5 micrograms) 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 micrograms) or perfused (1 micrograms 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 microgram 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 micrograms 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.
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001285:Atropine / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013189:SRS-A / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
chemical_list: D001095:Arachidonic Acids; D013189:SRS-A; D013931:Thromboxanes; D013928:Thromboxane A2; D001285:Atropine; D006632:Histamine