Selective effects of thiol reagents on the binding sites for imipramine and neurotransmitter amines in the rat brain

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Abstract
1 The action of the antithyroid drugs methimazole (MMI) and propylthiouracyl (PTU) on the binding of [3H]-imipramine, [3H]-5-hydroxytryptamine ([3H]-5-HT) (to 5-HT1-receptors) and [3H]-spiperone (to 5-HT2-, D2-receptors) of rat brain membranes has been examined. The synaptosomal uptake of [3H]-5-HT was also studied. 2 Micromolar concentrations of the disulphide bond reducing agents MMI, PTU, dithiothreitol (DTT) and mercaptoethanol increased both the binding of [3H]-imipramine and the uptake of [3H]-5-HT. In contrast, they decreased the number of 5-HT1-receptors, and did not affect 5-HT2- and D2-sites. 3 Reaction with membrane-bound sulphydryl (SH) groups by micromolar concentrations of N-ethylmaleimide (NEM), hydroxymercuribenzoic acid (PCMB), or Ellman's reagent (DTNB) decreased the binding of [3H]-imipramine, the number of 5-HT1-receptors, and the uptake of [3H]-5-HT. Millimolar concentrations of NEM were necessary in order to decrease partially 5-HT2- and D2-receptors. 4 The effects of NEM on imipramine recognition sites and on the uptake of 5-HT could be prevented by DTT; protection was not obtained in other receptor systems. 5 Three groups of receptors have been, thus, postulated, based upon their different sensitivity towards alterations in membrane [disulphide bridges SH] equilibrium: Group I, including imipramine recognition sites and the uptake system for 5-HT; Group II, including 5-HT]-receptors; Group III, including 5-HT2- and D2-receptors.