Uses
Astressin has been used as a CRF-receptor antagonist to study its effects on the decrease in the Schaffer collateral-CA1 field potential induced by hypoxia/hypoglycemia (ischemia) in rat hippocampal slices.
Definition
ChEBI: A 30-membered homodetic cyclic peptide comprising the sequence D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Glu-Ala-His-Lys-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2 cyclised by an amide bridge,
ormed by condensation of the side-chain carboxy group of the Glu residue at position 19 and the side-chain amino group of the Lys residue at position 22.
Biochem/physiol Actions
Astressin is a non-selective corticotropin releasing factor (CRF)-receptor antagonist. It potentially blocks CRF-induced adrenocorticotropic hormone (ACTH) release. Astressin effectively deceases delayed effects of chronic social isolation such as anxiety and fobial states in rats.
Enzyme inhibitor
This novel CRF antagonist (MW = 3663.20 g/mol; CAS 170809-51-5; Sequence: D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala- Glu-Gln-Ala-Gln-cyclo-(g-Glu-Ala-His-e-Lys)Asn-Arg-Leu-Leu-Mle-Glu- Ile-Ile-NH2; Solubility: 1 mg/mL in Acetic acid/water (10% vol/vol); Alternate Name: [D-Phe 12 , Nle 21,38 , Glu30 , Lys 33 ]-CRF) targets human Corticotropin-Releasing hormone (CRH) Receptor subtypes CRF2α (Ki = 1.5 nM) and CRF2β (Ki = 1 nM), with a comparable value (2 nM) for CRF1. (See also Antisauvagine-30; K41448) These type-2 GPCRs reside in plasma membranes of hormone-sensitive cells and bind CRH, a peptide hormone and neurotransmitter involved in stress responses. Astressin is a structurally constrained and competitive antagonists of corticotropin- releasing factor. Astressin is neuroprotective in the hippocampus when administered after a seizure. Peripheral injection of astressin blocks peripheral CRF- and abdominal surgery-induced delayed gastric emptying in rats. A related antagonist is Astressin 2B (FW = 4041.69 g/mol; CAS 681260-70-8; Sequence: Ac-Asp-Leu-Ser-D-Phe-His-a-methyl-Leu-Leu- Arg-Lys-Nle-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala- cyclo-(g-Glu-Ala-Asn-e-Lys)Leu-Leu-Leu-Asp-a-methyl-Leu-Ile-NH2). Astressin 2B is a potent and selective antagonist of CRF2 (IC50 = 1.3 nM) and CRF1 (IC50 > 500 nM).
