Isolation and structure of corticostatin peptides from rabbit fetal and adult lung.
A 34-amino acid peptide and three other structurally related peptides were isolated from rabbit fetal and adult lung. These cationic arginine- and cysteine-rich peptides inhibit corticotropin (ACTH)-stimulated rat adrenal cell corticosterone production. The peptide was called corticostatin (CSI). CSI was purified by reverse-phase HPLC and was shown to be homogenous from its amino acid analysis. Its sequence was determined on a gas-phase sequenator. The structure of CSI is Gly-Ile-Cys-Ala-Cys-Arg-Arg-Arg-Phe-Cys-Pro-Asn-Ser-Glu-Arg-Phe-Ser-Gly- Tyr-Cys - Arg-Val-Asn-Gly-Ala-Arg-Tyr-Val-Arg-Cys-Cys-Ser-Arg-Arg. CSI was found to markedly inhibit ACTH-stimulated corticosterone production by rat adrenal cells in vitro but did not affect basal levels. CSI did not affect the stimulation of aldosterone synthesis by angiotensin II in rat zona glomerulosa cells but it did suppress ACTH-stimulated aldosterone synthesis in whole adrenal cells, demonstrating that CSI is a specific inhibitor of ACTH-stimulated corticosteroid synthesis. The minimum effective concentration of CSI inhibiting ACTH-stimulated (33 pM) corticosterone production was 5 nM (20 ng/ml), the ED50 (50% effective dose) was 25 nM and steroidogenesis was completely inhibited at concentrations greater than 500 nM (2 micrograms/ml).
Zhu
Q Z
QZ
Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Hu
J
J
Mulay
S
S
Esch
F
F
Shimasaki
S
S
Solomon
S
S
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D005333:Fetus; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000032:analysis*; D008969:Molecular Sequence Data; D010455:Peptides / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D000596:Amino Acids; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone