Decreased muscarinic binding sites in small intestine from mice treated with neostigmine

It has been reported by several authors that animals given repeated sublethal doses of an organophosphate, acetylcholinesterase (AChE) inhibitor, develop tolerance to its toxicity. This phenomenon seems to be due, at least partially, to a decrease of central and peripheral cholinergic receptors. In the present study, we report that a decrease of muscarinic receptors, as measured by [³H]-quinuclidinyl benzilate (³H-QNB) binding, occurs in the small intestine of mice treated with the carbamate, AChE inhibitor, neostigmine. Male mice were given neostigmine in the drinking water at daily increasing concentrations (from 20 to 1000 ppm). Methylatropine (20mg/kg, i.p.) was administered twice a day for the same period to two groups of control and neostigmine-treated animals. AChE activity was inhibited 60–70% in small intestine and diaphragm and [³H]-QNB binding was significantly reduced in the small intestine of neostigmine-treated mice; both the number of receptors and the affinity were lower than control. This decrease was not present in the tissue of mice given methylatropine together with neostigmine. Administration of methylatropine alone caused a significant increase of [³H]-QNB binding in the small intestine.