Interleukin-1 receptors in mouse brain: Characterization and neuronal localization

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Endocrinology; (USA)

DOI:https://doi.org/10.1210/endo-127-6-3070· OSTI ID:6275825

Takao, T; Tracey, D E; Mitchell, W M; De Souza, E B ^[1]

---

1. National Institute on Drug Abuse, Baltimore, MD (USA)

The cytokine interleukin-1 (IL-1) has a variety of effects in brain, including induction of fever, alteration of slow wave sleep, and alteration of neuroendocrine activity. To examine the potential sites of action of IL-1 in brain, we used iodine-125-labeled recombinant human interleukin-1 (( 125I)IL-1) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) hippocampus and to study the distribution of IL-1-binding sites in brain using autoradiography. In preliminary homogenate binding and autoradiographic studies, (125I)IL-1 alpha showed significantly higher specific binding than (125I)IL-1 beta. Thus, (125I)IL-1 alpha was used in all subsequent assays. The binding of (125I)IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant value of 114 +/- 35 pM and a maximum number of binding sites of 2.5 +/- 0.4 fmol/mg protein. In competition studies, recombinant human IL-1 alpha, recombinant human IL-1 beta, and a weak IL-1 beta analog. IL-1 beta +, inhibited (125I)IL-1 alpha binding to mouse hippocampus in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constants of 55 +/- 18, 76 +/- 20, and 2940 +/- 742 pM, respectively; rat/human CRF and human tumor necrosis factor showed no effect on (125I)IL-1 alpha binding. Autoradiographic localization studies revealed very low densities of (125I)IL-1 alpha-binding sites throughout the brain, with highest densities present in the molecular and granular layers of the dentate gyrus of the hippocampus and in the choroid plexus. Quinolinic acid lesion studies demonstrated that the (125I)IL-1 alpha-binding sites in the hippocampus were localized to intrinsic neurons.

• OSTI ID: 6275825
• Journal Information: Endocrinology; (USA), Journal Name: Endocrinology; (USA) Vol. 127:6; ISSN ENDOA; ISSN 0013-7227
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL COMPOSITION
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LYMPHOKINES
MAMMALS
MAN
MEMBRANE PROTEINS
MEMBRANES
MICE
MITOGENS
NERVE CELLS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
VERTEBRATES