Isolation and biological activity of corticostatic peptides (anti-ACTH).
Corticostatins (CS's) are a family of low molecular weight peptides, rich in arginine and cysteine with the ability to inhibit ACTH stimulated adrenocortical steroidogenesis. They show a high degree of specificity in that they do not inhibit the action of angiotensin II in the adrenal cortex. Four corticostatins have been isolated from rabbit lung extracts and peritoneal neutrophil extracts and one from human neutrophils. Among them corticostatin I, CSI, is the most potent with an I.D.50 of 25 nM. Corticostatin activity is different from other published inhibitory factors such as TGF-B and ANF, which inhibit basal and angiotensin II stimulated steroidogenesis. Other factors such as macrophage secreted products, and septic shock plasma factors which have not been fully characterized also have suppressive activity on ACTH induced adrenocortical steroidogenesis in vitro. It is not yet clear whether there is any relationship between corticostatins and these macrophage products and shock plasma factor. Corticostatins do not inhibit dbcAMP induced steroidogenesis, however they do inhibit the accumulation of cAMP in response to ACTH in rat adrenal cell suspensions. Binding studies show that CSI is a competitive inhibitor of ACTH, probably acting by blocking, the address recognition site of the receptor. There is wide variation in the potency of the corticostatins ranging from an ID50 of 100 ng/ml for CSI to a completely inactive analog, HP1. In this paper we will describe the purification of the corticostatins and some recent results obtained on their mechanism of action.
Zhu
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Q
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Bateman
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Singh
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Solomon
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D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003345:Corticosterone / Q000096:biosynthesis; D006801:Humans; D007106:Immune Sera; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000502:physiology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology; D010455:Peptides / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
D007106:Immune Sera; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone