IRREVERSIBLE INHIBITORY EFFECT OF ATROPINE ON CONTRACTILE RESPONSES TO DRUGS IN ISOLATED RABBIT ILEUM

Effect of atropine sulfate (atropine) on the contractile responses to acetylcholine chloride (ACh), potassium chloride (K) and barium chloride (Ba) was investigated in isolated rabbit ileum. Tension of the strips suspended in the bath medium (Locke solution, 30 degrees C) was isotonically recorded. The K(ED50)- and Ba(ED50)-induced contractions were not affected by atropine at 3.0 X 10(-4) mM, which reversibly abolished the ACh(ED100)-contraction. After washout of 6.0 X 10(-4) mM atropine, the phasic, but not the tonic, component of ACh(ED50)-, K(ED50)- and Ba(ED50)- contractions was to some extent inhibited irreversibly. On the contrary, such irreversible inhibition of the phasic component was not produced by atropine methylbromide even in the high concentration of 3.0 X 10(-3) mM. The irreversible inhibitions by atropine of 6.0 X 10(-4) mM on the phasic component of ACh- and K-contractions were protected by pretreatment with a high concentration of ACh or K. Further, these irreversible inhibitions by atropine were potentiated by the absence of Ca and were abolished by the increase of Ca content in bath media. These results suggest that the irreversible inhibition of the contractile responses to drugs by atropine in high concentration may be due to the interference with the mobilization of Ca in the deep layer of the membrane, rather than by a blockade of muscarinic receptor sites.