Comparative protective effect of the inhaled β 2-agonist salbutamol (albuterol) on bronchoconstriction provoked by histamine, methacholine, and adenosine 5′-monophosphate in asthma

We have investigated the ability of salbutamol to protect against bronchoconstriction induced by methacholine, histamine, and adenosine 5′-monophosphate (AMP) in nine subjects with asthma. In a double-blind, placebo-controlled study, salbutamol, 2.5 mg administered by nebulization, increased the geometric mean provocation concentrations of methacholine, histamine, and AMP required to produce a 20% decrease in FEV 1 from 0.3 to 2.2, 0.4 to 3.8, and 4.0 to 106.7 mg/ml after placebo and active treatment, respectively ( p < 0.01). Thus, this dose of β 2-adrenoceptor agonist displaced the concentration-response curves for methacholine, histamine, and AMP to the right in a parallel fashion by 8.8 (0.6 to 29.3)-, 10.3 (1.4 to 33)-, and 26.6 (1.5 to 76.6)-fold, respectively, the difference between the results for AMP and those for histamine and methacholine being statistically significant ( p < 0.07). For six of the nine subjects studied, salbutamol displaced the concentration-response curve for AMP to the right by >50-fold. There was no correlation between bronchodilatation and protection against bronchoconstriction induced by any of the agonists. We conclude that salbutamol protects against bronchoconstriction provoked by methacholine and histamine by functional antagonism, whereas with AMP, an additional activity is demonstrable, possibly involving inhibition of mast cell-mediator release.