The interaction of acetylcholine and histamine on human bronchial smooth muscle contraction

The interaction of histamine (Hist) and acetylcholine (ACh) on human isolated bronchial smooth muscle (HIBSM) contraction, and the influence of the epithelium, was assessed using HIBSM obtained from 15 patients undergoing thoracotomy. Cumulative concentration effect curves for ACh and Hist, together with combinations of equipotent concentrations of both agonists, were generated using both epithelium-intact and epithelium-denuded HIBSM. In epithelium-denuded HIBSM both ACh (p less than 0.05) and Hist (p less than 0.005) produced a significantly enhanced maximal response and a 2.1 fold increase in the potency of ACh (p less than 0.02, n = 13). When ACh and Hist were added simultaneously, in equipotent concentrations, to epithelium-intact HIBSM, a significantly less (p less than 0.0005, n = 13) than additive response occurred with only 60% of the predicted maximum response being observed. However, following epithelium removal, an additive interaction between the two agonists (n = 8) occurred. Using HIBSM from five of the original 15 patients, similar experiments were performed to determine the influence of the muscarinic receptor antagonist atropine (0.1 microM) and the H1 receptor antagonist mepyramine (10 microM). Both resulted in a significantly less than additive interaction (40-50% of predicted tensions). Similar experiments were also performed in the presence of the cyclo-oxygenase inhibitor indomethacin (5 microM) and these failed to reverse the inhibition observed in HIBSM contraction (n = 5). The inhibitory interaction between ACh and Hist appears to be epithelium dependent and is not mediated via the release of prostanoids. Thus, there appears to be a complex interaction between contractile agonists and the epithelium, which is not just a simple summation of the activation of individual receptors on HIBSM.