Human blood-brain barrier insulin-like growth factor receptor
Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of /sup 125/I-IGF-1, /sup 125/I-IGF-2, and /sup 125/I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin.
- Research Organization:
- Univ. of California, Los Angeles (USA)
- OSTI ID:
- 5357952
- Journal Information:
- Metab., Clin. Exp.; (United States), Vol. 37:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
RECEPTORS
INSULIN
BIOLOGICAL MODELS
BLOOD-BRAIN BARRIER
CAPILLARIES
IODINE 125
MAN
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques