title: Selective effects of thiol reagents on the binding sites for imipramine and neurotransmitter amines in the rat brain.
abstract: The action of the antithyroid drugs methimazole (MMI) and propylthiouracil (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. 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. 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. 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. Three groups of receptors have been, thus, postulated, based upon their different sensitivity towards alterations in membrane [disulphide bridges in equilibrium SH] equilibrium: Group I, including imipramine recognition sites and the uptake system for 5-HT; Group II, including 5-HT1-receptors; Group III, including 5-HT2-and D2-receptors.
authors.forename: R
authors.initials: R
authors.lastname: Biassoni
authors.forename: A
authors.initials: A
authors.lastname: Vaccari
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D007099:Imipramine / Q000378:metabolism; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D008713:Methimazole / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D006902:Hydroxymercuribenzoates; D011954:Receptors, Dopamine; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D013439:Sulfhydryl Reagents; C027775:imipramine receptor; C030601:4-hydroxymercuribenzoate; D012701:Serotonin; D013134:Spiperone; D008713:Methimazole; D008623:Mercaptoethanol; D011441:Propylthiouracil; D004228:Dithionitrobenzoic Acid; D005033:Ethylmaleimide; D007099:Imipramine; D004229:Dithiothreitol