U46619 and carbocyclic thromboxane A2-induced increases in tracheal mucous gel layer thickness

U46619 or carbocyclic thromboxane A2 (CTA2) administered intravenously (IV) to rats produced dose-related increases of tracheal mucous gel layer thickness. Significant gel thickening was observed at doses ranging from 3.5 pg to 35 ng and from 500 pg to 50 ng for U46619 and CTA2, respectively. Intravenous treatment with pinane thromboxane A2 (PTA2), a thromboxane antagonist, prior to injection of U46619 or CTA2 attenuated the mucous gel layer response. The effect of PTA2 on U46619 and CTA2 was dose-dependent over the dosage range of PTA2 tested (1.0-31.6 micrograms/kg). PTA2 was equiactive against U46619 and CTA2 stimulated increases in gel thickness (ED50's 6.64 and 6.43 micrograms/kg respectively) suggesting a similar site of action for U46619 and CTA2. Slow reacting substance (SRS) injected IV into rats stimulated mucous gel layer thickening that was also inhibited by pretreatment with PTA2. These findings lend further support for the role of thromboxane in pathophysiologic conditions in which bronchorrhea contributes to the symptomatology.