PANCURONIUM MASKS THE PREJUNCTIONAL MUSCARINIC AUTORECEPTOR IN GUINEA-PIG TRACHEAL SMOOTH-MUSCLE

The effect of pancuronium pretreatment on the function of the prejunct ional muscarinic receptor in guinea-pig trachea was studied by using e lectrical field stimulation (EFS). The effects of cumulative doses of the muscarinic M(2) receptor antagonist gallamine were investigated in tracheal smooth muscle strips from guinea-pigs after addition of panc uronium in vitro and in strips from guinea-pigs which had been pretrea ted with doses of pancuronium that caused 100% neuromuscular blockade. The results of both types of experiments were compared to those of co ntrol groups of the same size. in all strips a dose response curve wit h cumulative doses of methacholine was made before EFS was switched on . No differences were found between the mean pD(2) value and slope of the concentration-response curves of untreated guinea-pigs and animals treated with anaesthetics and pancuronium. The animals showed variabl e responses to pancuronium. The bath concentration of pancuronium whic h decreased the EFS-induced contraction to half the original value var ied between 14 - 61 mu M. The intravenous dose necessary to paralyze t he muscles, varied among the different guinea-pigs from 0.017 - 0.O85 mg-kg(-1). The EFS-induced contraction for the concentration range of gallamine 0.32 mu M-0.32 mM was found to differ significantly between the strips treated with pancuronium in the organ bath and their contro l group. For the guinea-pigs anaesthetized and pretreated with pancuro nium a significant difference with control was observed at gallamine c oncentrations ranging from 0.032-0.32 mM. These results show that panc uronium, added to the organ bath as well as administered intravenously to the guinea-pig, masked the inhibitory muscarinic receptor.