Abstract
In order to study the sensitivity of acetylcholine (ACh) receptors exposed to anticholinesterase drugs, the ionophoretically evoked end-plate currents (e.p.c.i) in frog sartorius muscle were studied. During treatment with prostigmine (PST, 3 microM) or methanesulfonyl fluoride (MSF, 1-2 mM), the amplitude of the e.p.c.i evoked by ACh was first increased, reaching its maximum (200-400%) after 20-30 min and then decreased. If these experiments were repeated by applying carbachol (CCh) instead of ACh, an increase, although less pronounced (30-100%), was also observed. The results obtained by applying CCh cannot be ascribed to the inhibition of ACh-esterase, as CCh is not hydrolysed by this enzyme. Therefore, a direct action of both drugs on the ACh-receptor channel complex is suggested. From the comparison of the effects of PST and MSF on the responses to CCh and ACh applications, it is calculated that 20-25% of the increased response to ACh during PST treatment can be ascribed to the direct effect on the ACh-receptor channel complex. During MSF treatment, this amount results in 13-15%. The changes of the time course of the e.p.c.i (evoked by CCh or ACh), which is prolonged in the presence of PST and shortened during the maximum effect of MSF, suggest that the direct action of both studied drugs is different.
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