Hormonal and drug effects on the degradation of human myelin basic protein peptide 43-88 by alkaline proteolytic activity in the rat kidney.
The microsomal brush-border fraction of rat renal tissue contains enzymatic activity, optimally active at pH 9, that is capable of degrading human myelin basic protein (BP) peptide 43-88. In the present study, this degradation and the effect on it of selected drugs and hormones were examined further. Of the substances tested, 10(-2) M chloroquine and 10(-5) M ACTH 1-24 were found to be the most effective inhibitors followed by 10(-5) M ACTH 1-39; parathormone, glucagon and insulin were found to be inhibitors an order of magnitude weaker than ACTH 1-24. Hydrocortisone, dexamethasone, maleic acid and ACTH 4-10 were found to have minimal or no inhibitory effect on the peptide degrading activity. Gel filtration of the degradation products indicated that the rate of degradation of BP peptide 43-88 at pH 9 had been retarded by ACTH 1-24. These studies indicate that the clearance and catabolism of this peptide may be altered by available therapeutic agents.
Trestman
R L
RL
Heinemann
M A
MA
Whitaker
J N
JN
Seyer
J M
JM
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D011232:Chemical Precipitation; D002738:Chloroquine / Q000494:pharmacology; D002850:Chromatography, Gel; D010450:Endopeptidases / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007120:Immunochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011480:Protease Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D005938:Glucocorticoids; D006728:Hormones; D007328:Insulin; D008298:Maleates; D004676:Myelin Basic Protein; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011480:Protease Inhibitors; C037147:myelin basic protein 43-88; D002738:Chloroquine; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; C030272:maleic acid; D010450:Endopeptidases