Specific uptake of a behaviorally potent [3H]ACTH4-9 analog in the septal area after intraventricular injection in rats.
Distribution within the brain of a behaviorally potent [3H]ACTH4-9 analog 2 h after intraventricular injection in rats was studied in the presence and absence of behaviorally and structurally similar peptides, to explore the significance of earlier found preferential uptake of the [3H]ACTH4-9 analog in the septal area. Hypophysectomy resulted in significantly enhanced uptake of radioactivity in the septum as compared to normal rats. No increase in this brain area of hypophysectomized rats was observed after intraventricular injection of [3H]Phe. Elevated circulating ACTH levels after adrenalectomy seemed too low to compete with the septal uptake of the ACTH4-9 analong. Subcutaneous substitution of hypophysectomized rats with sustained release zinc phosphate preparations of the behaviorally equipotent peptides ACTH1-24 and ACTH4-10 decreased the accumulation of the [3H]ACTH4-9 analog in the septum, whereas treatment with the behaviorally inactive fragment ACTH11-24 is not effective. Retreatment of hypophysectomized rats with neuropeptides, differing structurally from natural ACTH peptides (7-D-Phe-ACTH4-10, BETA-LPH61-76 and 9-desglycinamide, 8-Lys-vasopressin), did not change the uptake of the ACTH4-9 analog in any of the investigated brain areas. These results give evidence for specific uptake of the ACTH4-9 analog in the septal region, because competitive displacement occurs only with peptides which both behaviorally and structurally are closely related to the ACTH4-9 analog.
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D007016:Hypophysectomy; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D010649:Phenylalanine / Q000494:pharmacology; D011149:Pons / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D012688:Septum Pellucidum / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013788:Thalamus / Q000378:metabolism
D010649:Phenylalanine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone