INCREASED HISTAMINE Hi RECEPTOR BLOCKADE BY CHLORPHENIRAMINE IN TRACHEAL CHAINS OF ASTHMATIC GUINEA PIGS

Receptor affinity and drug delivery to the receptor sites could be determinant factors for the increased bronchial responsiveness seen in asthma. Competitive antagonism blockade which is measured as dose ratio-l (DR-I) depends only on these two factors. Therefore, in this study we have examined histamine HI blockade by chlorpheniramine on isolated tracheal chains of asthmatic compared to control guinea pigs. An experimental model of asthma was induced in guinea pigs by injection and inhalation of ovalbumin (OA), and tracheal chains of asthmatic and control animals (for each group n= 12) were prepared. The responses of tracheal chains to cumulative concentrations of histamine (H) in the absence and presence of 5 nM chlorpheniramine was measured, and the effective concentration of H causing 50% of maximum response (ECso H) was obtained. The chlorpheniramine blockade (DR-I) was calculated by (post chlorpheniramine EC50H/EC50 H)-1. The response of tracheal chains to 0.1 % OA relative to the contraction obtained by 10 mM methacholine was also measured. The tracheal response of asthmatic guinea pigs to OA was significantly higher than that of control animals (mean ± SEM, 57.03±4.99 VS. 3.92±1 .14, p<O.OO l ). Histamine HI receptor blockade by chlorpheniramine (DR-I) was also significantly higher in tracheas of asthmatic compared to control animals (1 7 .34±3.8 9vs. 4.1I±I.08, p<0.01). There was a significant correlation between (DR-I) and tracheal responses to OA (r= 0.51 ,p<0.05). This enhanced histamine HI receptor blockade in tracheal chains of asthmatic animals confirms our previous findings which was predicted to be due to increased drug delivery to the receptor. Drug delivery could also be a determinant factor for bronchial responsiveness to most stimulating agents in asthma.