Date of Award


Degree Type


Degree Name

Doctor of Philosophy


In order to ascertain a role of histamine (HM) in the mediation of induced asthma, HM and Diamine Oxidase activity (DAO) were determined serially in plasma together with the Forced Expiratory Volume in the first second (FEV(,1)) in 18 subjects inhaling methacholine(MCH) by increments to permissible limits of 224 cumulative units (cu). HM was measured in plasma ultrafiltrates by an isotropic assay based upon the specificity of HM-N-methyltransferase harvested from rat brains. DAO was determined with o-dianisidine in plasma buffered at pH 7.4. Thirteen asthmatics were bronchial Responders. The provocative dose of MCH yielding a 20% FEV(,1) fall (PD(,20) -FEV(,1)) ranged from 1.3 to 220 cu. Maxima for plasma HM were found at variable stages; when grouped separately according to their occurrence during and after inhalation of the highest MCH increment, these maxima were in each instance significantly higher (P 50 cu). This suggests that bronchial sensitivity to this cholinergic agent may be unrelated to the magnitude of HM release from lung. In only 1 Responder (PD(,20)-FEV(,1) = 78 cu) did plasma DAO and FEV(,1) correlate directly (P < 0.01; n =12), the lowest value of both coinciding with the highest (95ng/ml) of 3 prominent plasma HM spikes. From parallel in vitro work, MCH emerged as an inhibtor of plasma DAO under diverse conditions. This suggests that delayed HM degradation may be a hitherto unappreciated MCH effect contributing to bronchospasm when this cholinergic agent is inhaled.



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