Characterization of a neurokinin B receptor site in rat brain using a highly selective radioligand

Journal Article · Tue Aug 05 00:00:00 EDT 1986 · J. Biol. Chem.; (United States)

OSTI ID:5127609

Laufer, R; Gilon, C; Chorev, M; Selinger, Z

We have recently characterized a tachykinin receptor subtype (SP-N) whose preferred ligand is the mammalian neuropeptide, neurokinin B. To investigate this novel tachykinin receptor, we have now prepared a radiolabeled peptide, N alpha-(( /sup 125/I)desamino-3-iodotyrosyl)-(Asp5,6, N-methyl-Phe8)substance P (5-11) heptapeptide (/sup 125/I-BH-NH-Senktide), which selectively interacts with the SP-N receptor subtype. The binding of /sup 125/I-BH-NH-Senktide to rat cerebral cortex membranes was studied under conditions that minimized nonspecific binding. Unlike other tachykinin receptor probes, this radioligand is not degraded during the binding experiment. Binding of /sup 125/I-BH-NH-Senktide is reversible, saturable, and of high affinity (KD = 0.9 nM). The radioligand labels a single class of binding site (122 fmol binding sites/mg of protein), as indicated by a linear Scatchard plot and a Hill coefficient close to unity (nH = 1.05). The pharmacological specificity of this binding site corresponds to that of the neuronal SP-N receptor in guinea pig ileum myenteric plexus, which was determined by a functional bioassay. Among various rat brain regions, the highest binding was observed in the cerebral cortex, olfactory bulb, hypothalamus, and hippocampus. These results suggest the existence and specific distribution of a neurokinin B receptor site of the SP-N type in rat brain. /sup 125/I-BH-NH-Senktide is the first selective and potent probe for this receptor and is thus an important tool for further studies of its distribution, regulation, and functional role.

• Research Organization: Hebrew Univ. of Jerusalem, Israel
• OSTI ID: 5127609
• Journal Information: J. Biol. Chem.; (United States), Vol. 22
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
KININS
RADIORECEPTOR ASSAY
RECEPTORS
BRAIN
GUINEA PIGS
HAMSTERS
IODINE 125
LABELLED COMPOUNDS
RATS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques