[The inactivation of specific type-II glucocorticoid receptors by preparations of the phenothiazine series].
Experiments were conducted on adrenalectomized and intact male Wistar rats weighing 100-120 g. Hepatic cytosol was obtained by ultracentrifugation. Specific type-II or -III glucocorticoid receptors were determined by means of labeled triamcinolone acetonide or labeled cortisol. In model studies aminazin (chlorpromazine hydrochloride) and tisercin (levomerpromazine) were used in concentrations of 3.5 x 10(-4) M, and phrenolon in a concentration of 1.0 x 10(-4) M. Adrenalectomized and intact animals were given intraperitoneal injection of 0.1 ml/100 g of 2.5% tisercin solution. In model experiments and in intraperitoneal administration to adrenalectomized and intact animals aminazin and tisercin caused inactivation of specific type-II glucocorticoid receptors of liver cytosol. In model experiments only tisercin in a concentration of 7.0 x 10(-4) M increased the level of type-III glucocorticoid receptor of hepatic cytosol of adrenalectomized rats. Preliminary treatment of type-II glucocorticoid receptors of liver cytosol with tisercin (1.0 x 10(-4) M and 1.0 x 10(-3) M) and subsequent removal of tisercin by hard-phase adsorption from the cytosol led to their inactivation. The author was the first to prove that some therapeutic agents of the phenothiazine series are capable of inactivating hepatic glucocorticoid receptors of adrenalectomized and intact animals. The theoretical and practical significance of the discovered effect of agents of the phenothiazine series is discussed.
Golikov
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D000315:Adrenalectomy; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005938:Glucocorticoids / Q000378:metabolism; D008297:Male; D010640:Phenothiazines; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; D005938:Glucocorticoids; D010640:Phenothiazines; D011965:Receptors, Glucocorticoid
Inaktivatsiia spetsificheskikh gliukokortikoidnykh retseptorov II tipa preparatami fenotiazinovogo riada.