Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus

Science ◽  
1980 ◽  
Vol 207 (4435) ◽  
pp. 1081-1083 ◽  
Author(s):  
M van Houten ◽  
B. Posner ◽  
B. Kopriwa ◽  
Brawer
Keyword(s):  
Median Eminence ◽  
Binding Sites ◽  
Arcuate Nucleus ◽  
Insulin Binding ◽  
Nerve Terminals

Ultrastructural Localization of Acetylcholinesterase in the Arcuate Nucleus and Median Eminence of the Rat

1977 ◽  
Vol 35 ◽  
pp. 440-441
Author(s):  
K.A. Carson ◽  
C.B. Nemeroff ◽  
M.S. Rone ◽  
J.S. Kizer ◽  
J.S. Hanker
Keyword(s):  
Choline Acetyltransferase ◽  
Median Eminence ◽  
Arcuate Nucleus ◽  
Cholinergic Neurons ◽  
Ultrastructural Localization ◽  
Male Rats ◽  
Neonatal Rats ◽  
Good Marker ◽  
Chemical Studies ◽  
High Doses

Biochemical, physiological, pharmacological, and more recently enzyme histo- chemical data have indicated that cholinergic circuits exist in the hypothalamus. Ultrastructural correlates of these pathways such as acetylcholinesterase (AchE) positive neurons in the arcuate nucleus (ARC) and stained terminals in the median eminence (ME) have yet to be described. Initial studies in our laboratories utilizing chemical lesioning and microdissection techniques coupled with microchemical and light microscopic enzyme histo- chemical studies suggested the existence of cholinergic neurons in the ARC which project to the ME (1). Furthermore, in adult male rats with Halasz deafferentations (hypothalamic islands composed primarily of the isolated ARC and the ME) choline acetyltransferase (ChAc) activity, a good marker for cholinergic neurons, was not significantly reduced in the ME and was only somewhat reduced in the ARC (2). Treatment of neonatal rats with high doses of monosodium 1-glutamate (MSG) results in a lesion largely restricted to the neurons of the ARC.

[3H]nicotine binding sites are associated with mammalian optic nerve terminals

1988 ◽  
Vol 1 (2) ◽  
pp. 245-248 ◽  
Author(s):  
Glen T. Prusky ◽  
Max S. Cynader
Keyword(s):  
Optic Nerve ◽  
Visual System ◽  
Nicotinic Acetylcholine Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Optic Tract ◽  
Nerve Fibers ◽  
Nerve Terminals ◽  
Nicotinic Acetylcholine ◽  
Retinotectal Transmission

AbstractThe autoradiographic distribution of [3H]nicotine binding sites was examined in the superior colliculus in normal rats and cats, and in animals in which one or both eyes were removed. [3H]Nicotine binding sites in normal animals were densely concentrated in the superficial layers of the colliculus corresponding to the zone of termination of optic nerve fibers. Following bilateral enucleation, [3H]nicotine binding in the superficial collicular layers was drastically reduced. Unilateral enucleation markedly reduced [3H]nicotine binding sites in the colliculus contralateral to the removed eye, with little effect on the ipsilateral colliculus. These results provide further evidence that nicotinic acetylcholine receptors have a presynaptic location on optic tract terminals and may therefore modulate retinotectal transmission in both the rat and cat visual system.

scholarly journals Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain

2019 ◽  
Author(s):  
Theresia Gutmann ◽  
Ingmar Schäfer ◽  
Chetan Poojari ◽  
Beate Brankatschk ◽  
Ilpo Vattulainen ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Binding Sites ◽  
Structural Model ◽  
Receptor Site ◽  
Insulin Binding ◽  
Proximal Region ◽  
Dynamics Simulation ◽  
Structural Basis ◽  
Structure Based Drug Design ◽  
Receptor Interactions

AbstractGlucose homeostasis and growth essentially depend on the peptide hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand–receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have only resolved site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we determined the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin–site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis enabling a comprehensive description of ligand–receptor interactions that ultimately will inform new approaches to structure-based drug design.In briefA cryo-EM structure of the complete insulin receptor ectodomain saturated with four insulin ligands is reported. The structural model of the insulin–insulin receptor complex adopts a T-shaped conformation, reveals two additional insulin-binding sites potentially involved in the initial interaction of insulin with its receptor, and resolves the membrane proximal region.

Insulin receptors on Xenopus laevis oocytes: effects of injection of ob/ob mouse liver mRNA

1991 ◽  
Vol 100 (1) ◽  
pp. 167-171
Author(s):  
D.A. Diss ◽  
B.D. Greenstein
Keyword(s):  
Xenopus Laevis ◽  
Binding Sites ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Cell Types ◽  
Follicle Cells ◽  
Vitelline Membrane ◽  
Xenopus Laevis Oocytes ◽  
Endogenous Insulin ◽  
Order Of Magnitude

We describe here conditions for the detection of insulin binding sites on Xenopus laevis oocytes. The binding of 125I-labelled insulin displayed sigmoidal behaviour, which is characteristic of the binding relationship between insulin and its receptor. Resolution of the resulting curvilinear Scatchard plot into two components revealed KD values of 8.86 × 10(−10) +/− 1.9 × 10(−10) and 5.32 × 10(−9) +/− 2.4 × 10(−9) M and n values of 9.7 × 10(7) +/− 0.4 × 10(7) and 3.3 × 10(8) +/− 0.5 × 10(8) binding sites per oocyte, respectively. The possibility cannot be excluded, however, that receptors for IGF-1 were also being detected. Also described are conditions for the rapid and efficient removal of all tissues surrounding the oocyte, including the vitelline membrane. We could not detect any specific 125I-labelled insulin binding to oocytes that had their follicle cells or vitelline membrane removed and this was not due to the enzymic treatment used in the process. Microinjection of oocytes without follicular layers did not result in the appearance of any detectable insulin binding sites, which were, however, observed if oocytes were first stripped of the vitelline membrane. We suggest that oocytes may possess endogenous insulin receptors on their surface in numbers of the same order of magnitude as those present on somatic cells. The removal of tissues surrounding the oocyte should facilitate studies aimed at determining functional interactions of the various cell types during oocyte development and for studying insulin receptors on the oocyte-follicular cell complex.

scholarly journals Chloroquine augments the binding of insulin to its receptor

1995 ◽  
Vol 311 (3) ◽  
pp. 787-795 ◽  
Author(s):  
A P Bevan ◽  
J R Christensen ◽  
J Tikerpae ◽  
G D Smith
Keyword(s):  
Binding Sites ◽  
Slow Component ◽  
Insulin Binding ◽  
Dissociation Rate ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Binding Model ◽  
Binding Data ◽  
Plasma Membrane Receptor ◽  
Dissociation Rate Constants

The effect of chloroquine on the interaction of insulin with its receptor has been investigated under both equilibrium and non-equilibrium conditions. Chloroquine was found to augment insulin binding in a pH-dependent manner between pH 6.0 and pH 8.5, with the maximum occurring at approximately pH 7.0. Analysis of the equilibrium binding data in terms of independent binding sites gave equivocal results but suggested an increase in the high-affinity component. Analysis using the negative co-operativity binding model of De Meyts, Bianco and Roth [J. Biol. Chem. (1976) 251, 1877-1888] suggested that the affinity at both high and low occupancy was increased equally. The kinetics of association of insulin with the plasma-membrane receptor indicated that, although the net rate of association increased in the presence of chloroquine, this was due to a reduction in the dissociation rate rather than an increase in the association rate. This was confirmed by direct measurement of the rates of dissociation. Dissociation was found to be distinctly biphasic, with fast and slow components. Curve fitting suggested that the decrease in dissociation rate in the presence of chloroquine was not due to a decrease in either of the two dissociation rate constants, but rather to an increase in the amount of insulin dissociating by the slow component. It was also found that the increase in dissociation rate in the presence of excess insulin, ascribed to negative co-operativity, could be accounted for by an increase in the amount of insulin dissociating by the faster pathway, rather than by an increase in the dissociation rate constant. Thus chloroquine appears to have the opposite effect to excess insulin, and evidence was found for the induction of positive co-operativity in the insulin-receptor interaction at high chloroquine concentrations. Evidence was also found for the presence of low-affinity chloroquine binding sites with binding parameters similar to the concentration dependence of the chloroquine-induced augmentation of insulin binding.

Insulin Binding Sites Induced in the Tetrahymena by Rat Liver Receptor Antibody

1984 ◽  
Vol 39 (1-2) ◽  
pp. 183-185 ◽  
Author(s):  
G. Csaba ◽  
P. Kovács ◽  
Ágnes Inczefi-Gonda
Keyword(s):  
Rat Liver ◽  
Concanavalin A ◽  
Binding Sites ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Receptor Antibody ◽  
Receptor Antibodies

Abstract Tetrahvmena cells treated with purified rabbit anti­ bodies to rat hepatocellular membrane exhibited a consider­ able increase in binding capacity on reexposure to the antibody 24 h later. Insulin binding was similarly enhanced by preexposure to the antibody, and vice versa, preex­ posure to insulin enhanced the later binding of rat liver receptor antibodies. This suggests that (1) the Tetrahymena and the rat possess similar insulin receptors, and (2) the receptor antibody is also able to induce imprinting for itself as well as for insulin. Concanavalin-A, noted for binding overlap with insulin, failed to induce imprinting either for insulin or for antibodies to receptors, whereas the latter did induce imprinting for Concanavalin-A.

scholarly journals Identification of Host Insulin Binding Sites on Schistosoma japonicum Insulin Receptors

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159704 ◽  
Author(s):  
Rachel J. Stephenson ◽  
Istvan Toth ◽  
Jiening Liang ◽  
Amanjot Mangat ◽  
Donald P. McManus ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Binding Sites ◽  
Insulin Receptors ◽  
Insulin Binding
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