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Different effects of N-ethylmaleimide on M1 and M2 muscarine receptors in rat brain.

N-Ethylmaleimide (MalNEt) disclosed three differences between M2 muscarine receptors in membranes from the rat brainstem and M1 receptors in the hippocampus. At 0.1 mM, MalNEt completely interconverted the higher affinity state of M2 receptors for carbachol to a lower affinity state, while having no effect on the two affinity states of M1. This "uncoupling" effect is similar to that produced by guanine nucleotides and appears to be due to separation of an agonist-receptor complex from a guanine nucleotide-binding protein. Higher MalNEt concentrations (1-5 mM) increased the affinity of uncoupled M2 receptors, again without effect on M1 states. Finally, in MalNEt, the affinity of M2 receptors for carbachol was different from values for M1 receptors. Thus, MalNEt is an excellent agent for distinguishing M1 and M2 receptors and the two states of M2 receptors. MalNEt had no effect on the affinity or M1-selectivity of the antagonist pirenzepine.[1]


  1. Different effects of N-ethylmaleimide on M1 and M2 muscarine receptors in rat brain. Flynn, D.D., Potter, L.T. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
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