NDLI: Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

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Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

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Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Altar, C. A. Burton, L. E. Bennett, G. L. Dugich-djordjevic, M.
Description	Author Affiliation: Altar CA ( Department of Developmental Biology, Genentech, Inc., South San Francisco, CA 94080.);
Abstract	Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity (Kd 52-85 pM) and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	88
Language	English
Publisher	National Academy of Sciences
Publisher Date	1991-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Brain Metabolism Nerve Growth Factors Receptors, Cell Surface Animals Autoradiography Axons Drug Effects Physiology Binding Sites Binding, Competitive Iodine Radioisotopes Kinetics Genetics Pharmacology Organ Specificity Radionuclide Imaging Rats, Inbred Strains Receptors, Nerve Growth Factor Recombinant Proteins Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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