Study of an octadecaneuropeptide derived from diazepam binding inhibitor (DBI): biological activity and presence in rat brain

Journal Article · Sat Feb 01 04:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.3.827· OSTI ID:6410283

Ferrero, P; Santi, M R; Conti-Tronconi, B; Costa, E; Guidotti, A

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), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 83:3; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACID SEQUENCE
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZO COMPOUNDS
BIOCHEMISTRY
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHEMISTRY
DRUGS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MOLECULAR STRUCTURE
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDES
PROTEINS
RADIORECEPTOR ASSAY
RATS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES