Interactions of adrenocorticotropic hormone with its adrenal receptors. Degradation of ACTH-1-24 and ACTH-11-24.
Crude membranes (20,000 times g pellet) prepared from human, rat, and ovine adrenals bind 125-I-corticotropin-(1-24)-tetracosapeptide (125-I-ACTH-1-24) and degrade unbound hormone. The degradation is dependent on temperature and the concentration of membrane proteins. The degradation of 125-I-[9-tryptophan(o-nitrophenylsulfenyl)]-corticotropin-(1-24)-tetracosapeptide (125-I-NPS-ACTH-1-24) is similar to 125-I-ACTH-1-24, but that of 125-I-corticotropin-(11-24)-tetradecapeptide (125-I-ACTH-1-24 is inhibited by ACTH-1-24 and corticotropin-(1-10)-decapeptide (ACTH-1-10), but ACTH-11-24 at the same molar concentration has no effect. On the other hand, the degradation of 125-I-ACTH-11-24 is protected by ACTH-11-24 and ACTH-1-24, but not by ACTH-1-10. This suggests two systems of degradation, one will have the NH-2-terminal sequence of ACTH-1-24 as substrate, and the other the 11-24 COOH-terminal sequence. The main label product from the degradation of the 125-I-ACTH-1-24 and 125-I-ACTH-11-24 behaves as [125-I]monoiodotyrosine on Sephadex G-50 and paper chromatography. The independence of ACTH binding to its receptor and degradation is demonstrated by the following facts. (a) Calcium and pancreatic trypsin inhibitor completely inhibit the binding at concentrations when the degradation is not altered; (b) the sequences of peptides of ACTH which inhibit the binding and degradation of 125-I-ACTH-1-24 are different.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface; D012756:Sheep; D013696:Temperature; D014361:Trypsin Inhibitors / Q000494:pharmacology
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D014361:Trypsin Inhibitors; D000324:Adrenocorticotropic Hormone; D007931:Leucyl Aminopeptidase; D000262:Adenylyl Cyclases; D002118:Calcium