Agonist-specific reverse regulation of muscarinic receptors by transition metal ions and guanine nucleotides

Transition metal ions, e.g. Mn²⁺, Ni²⁺ and Co²⁺ enhance $\text{in vitro}$ agonist binding to muscarinic receptors in mouse cortex or hippocampus. This effect arises mainly from the conversion of low to high affinity binding sites. Binding properties of antagonists in these brain areas, as well as those of both agonists and antagonists of medulla-pons muscarinic receptors, are insensitive to these ions. The induced interconversion can be reversed by either of the following procedures: (i) removal of the ions; (ii) thermal exposure; (iii) addition of micromolar concentrations of guanine nucleotides.