Study of an octadecaneuropeptide derived from diazepam binding inhibitor (DBI): biological activity and presence in rat brain
An endogenous brain neuropeptide with 104 amino acid residues that modulates ..gamma..-aminobutyric acid receptor function was termed DBI because it displaces diazepam from its specific brain binding sites. Tryptic digestion of DBI generates an octadecaneuropeptide (ODN) that is more potent than the parent compound in the displacement of specifically bound ..beta..-(/sup 3/H)carboline-3-carboxylate methyl ester ((/sup 3/H)BCCM) and in proconflict action. The proconflict action of ODN is antagonized by the imidobenzodiazepinone Ro 15-1788, which is a specific antagonist of ..beta..-carboline and benzodiazepine recognition sites. The ODN amino acid sequence is Gln-Ala-Thr-Val-Gly-Asp-Val-Asn-Thr-Asp-Arg-Pro-Gly-Leu-Leu-Asp-Leu-Lys. The pharmacological properties associated with this sequence were confirmed by comparing the activity of ODN generated from tryptic digestion of DBI with that of ODN obtained by synthesis. In primary cultures of cerebellar granule cells of rat, DBI, ODN, octapeptide, heptapeptide, and hexapeptide preferentially displace (/sup 3/H)BCCM over (/sup 3/H)flunitrazepam; moreover, they displace bound (/sup 3/H)BCCM completely but (/sup 3/H)flunitrazepam only by 50%. These data suggest that ODN includes a specific ligand for the ..gamma..-aminobutyric acid receptor regulatory site occupied by ..beta..-carbolines. Using rabbit antibodies directed against the NH/sub 2/-terminal portion of ODN, the authors detected ODN-like material in rat brain homogenates. However, whether this material is identical to the ODN generated by tryptic digestion of DBI remains to be established.
- Research Organization:
- Fidia-Georgetown Institute for the Neurosciences, Washington, DC
- OSTI ID:
- 6410283
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 83:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AMINOBUTYRIC ACID
RADIORECEPTOR ASSAY
AZO COMPOUNDS
PEPTIDES
BIOCHEMISTRY
AMINO ACID SEQUENCE
BRAIN
NERVE CELLS
RATS
TRITIUM COMPOUNDS
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DRUGS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MOLECULAR STRUCTURE
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics