ANTICHOLINESTERASE DRUGS STIMULATE PHOSPHATIDYLINOSITOL RESPONSE IN RAT TRACHEAL SLICES

Some anticholinesterase (anti-ChE) drugs induce airway smooth muscle c ontraction. Whether anti-ChE drugs stimulate muscarinic receptors in a irway smooth muscle as well as nicotinic receptors in neuromuscular ju nction is unknown. Since there is a direct relationship between phosph atidylinositol (PI) response and airway smooth muscle contraction indu ced by muscarinic agonists, we examined the effects of neostigmine, ph ysostigmine, pyridostigmine, and edrophonium on PI response in the air way smooth muscle. The rat tracheal slices were incubated in Krebs-Hen seleit solution containing LiCl and [H-3]myo-inositol in the presence of carbachol, anti-ChE, or none of them. [H-3]inositol monophosphate ( IP1), which is a degradation product of PI response, was counted with a liquid scintillation counter. Inositol monophosphate accumulation wa s stimulated by neostigmine, physostigmine, and pyridostigmine in a do se-dependent manner, but was not affected by edrophonium. These increa ses were completely inhibited by atropine. The results suggest that ne ostigmine, physostigmine, and pyridostigmine stimulate PI response in the airway smooth muscle, which would cause bronchoconstriction, while edrophonium does not affect PI response.