Effects of soman on isolated human bronchi

The effect of pinacolyl methylphosphonofluoridate (soman) on human bronchi in vitro and the ability of a beta(2)-adrenoceptor agonist to relax contracture in human airways resulting from exposure to soman have been investigated. On unstimulated bronchi, soman produced variable effects. When bronchi were stimulated continuously by application of an electric field, soman produced sustained contracture in all tissues examined. Application of the beta(2)-adrenoceptor agonist isoproterenol elicited relaxations that were larger in magnitude than the contractions resulting from the actions of soman. The duration of the isoproterenol-induced relaxation was variable. Of 12 preparations examined, 3 showed a rapid reversal of relaxation with a T-1/2 of 14 +/- 1 min; 6 reversed more slowly with a T-1/2 of 106 +/- 6 min; and 3 showed no reversal of the relaxation within 120 min. In tissues having a rapid reversal time of relaxation, application of the M(2) muscarinic receptor antagonist []2-[(Diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AFDX-116) prolonged the response to isoproterenol. These observations demonstrate that beta(2)-adrenergic agonists antagonize both cholinergic responses to soman and the noncholinergic intrinsic tone that is quite pronounced in human bronchi. The ability of M(2) muscarinic receptor antagonists to prolong isoproterenol-induced relaxation suggests that human airway smooth muscle responses to beta-agonists are modulated by M(2) muscarinic receptors. Isolated human airway smooth muscle is therefore a useful model for the study of toxic chemical agent effects.