Opiate receptor function may be modulated through an oxidation-reduction mechanism

Science ◽  
1980 ◽  
Vol 208 (4448) ◽  
pp. 1171-1173 ◽  
Author(s):  
G Marzullo ◽  
B Hine
Keyword(s):  
Receptor Binding ◽  
Opiate Receptor ◽  
Reduction Mechanism ◽  
Receptor Function ◽  
Cupric Ion ◽  
Oxidation Reduction ◽  
Mechanism Of Oxidation

Cupric ion, a thiol oxidant, caused naloxone-reversible analgesia when injected intracerebroventricularly in mice; its potency was close to that of morphine. Dithiothreitol, a thiol reductant, reversed the analgesia induced by cupric ion and antagonized analgesia induced by morphine. Oxidized dithiothreitol had no effect. These findings, together with evidence for redox modification of opiate receptor binding in vitro, suggest that a mechanism of oxidation-reduction of thiols may modulate opiate receptor function.

BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers

1990 ◽  
Vol 259 (4) ◽  
pp. H1278-H1287 ◽  
Author(s):  
R. Kawai ◽  
Y. Sawada ◽  
M. Channing ◽  
A. H. Newman ◽  
K. C. Rice ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rank Order ◽  
Compartment Model ◽  
Brain Structures ◽  
Opiate Receptor ◽  
Brain Regions ◽  
Binding Model ◽  
Rapid Phase

The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.

Comparison of in vivo and in vitro parameters of opiate receptor binding in naive and tolerant/dependent rodents

Life Sciences ◽  
1975 ◽  
Vol 16 (12) ◽  
pp. 1823-1828 ◽  
Author(s):  
V. Höllt ◽  
J. Dum ◽  
J. Bläsig ◽  
P. Schubert ◽  
A. Herz
Keyword(s):  
Receptor Binding ◽  
Opiate Receptor

scholarly journals Stereotypic neutralizing VH antibodies against SARS-CoV-2 spike protein receptor binding domain in COVID-19 patients and healthy individuals

2021 ◽  
pp. eabd6990
Author(s):  
Sang Il Kim ◽  
Jinsung Noh ◽  
Sujeong Kim ◽  
Younggeun Choi ◽  
Duck Kyun Yoo ◽  
...  
Keyword(s):  
B Cells ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Binding Domain ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Healthy Individuals

Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 out of 17 patients with COVID-19 had stereotypic variable heavy chain (VH) antibody clonotypes directed against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were comprised of immunoglobulin heavy variable (IGHV)3-53 or IGHV3-66 and immunoglobulin heavy joining (IGHJ)6 genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different immunoglobulin heavy variable chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these VH clonotypes existed in six out of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.

scholarly journals Epitope–Paratope Interaction of a Neutralizing Human Anti-Hepatitis B Virus PreS1 Antibody That Recognizes the Receptor-Binding Motif

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 754
Author(s):  
Jisu Hong ◽  
Youngjin Choi ◽  
Yoonjoo Choi ◽  
Jiwoo Lee ◽  
Hyo Jeong Hong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Receptor Binding ◽  
Neutralizing Antibody ◽  
Hbv Infection ◽  
Binding Motif ◽  
Alanine Scanning Mutagenesis ◽  
B Virus ◽  
Complementarity Determining Regions

Hepatitis B virus (HBV) is a global health burden that causes acute and chronic hepatitis. To develop an HBV-neutralizing antibody that effectively prevents HBV infection, we previously generated a human anti-preS1 monoclonal antibody (1A8) that binds to genotypes A–D and validated its HBV-neutralizing activity in vitro. In the present study, we aimed to determine the fine epitope and paratope of 1A8 to understand the mechanism of HBV neutralization. We performed alanine-scanning mutagenesis on the preS1 (aa 19–34, genotype C) and the heavy (HCDR) and light (LCDR) chain complementarity-determining regions. The 1A8 recognized the three residues (Leu22, Gly23, and Phe25) within the highly conserved receptor-binding motif (NPLGFFP) of the preS1, while four CDR residues of 1A8 were critical in antigen binding. Structural analysis of the epitope–paratope interaction by molecular modeling revealed that Leu100 in the HCDR3, Ala50 in the HCDR2, and Tyr96 in the LCDR3 closely interacted with Leu22, Gly23, and Phe25 of the preS1. Additionally, we found that 1A8 also binds to the receptor-binding motif (NPLGFLP) of infrequently occurring HBV. The results suggest that 1A8 may broadly and effectively block HBV entry and thus have potential as a promising candidate for the prevention and treatment of HBV infection.

In vitro potency determination of botulinum neurotoxin B based on its receptor-binding and proteolytic characteristics

2016 ◽  
Vol 34 ◽  
pp. 97-104 ◽  
Author(s):  
Emina Wild ◽  
Ursula Bonifas ◽  
Jolanta Klimek ◽  
Jan-Hendrik Trösemeier ◽  
Beate Krämer ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Botulinum Neurotoxin ◽  
Botulinum Neurotoxin B

scholarly journals Tau antibody isotype induces differential effects following passive immunisation of tau transgenic mice

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Rinie Bajracharya ◽  
David Brici ◽  
Liviu-Gabriel Bodea ◽  
Phillip W. Janowicz ◽  
Jürgen Götz ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Microglial Activation ◽  
Fc Receptor ◽  
Passive Immunisation ◽  
Antibody Isotype ◽  
Passive Immunotherapy ◽  
Microglial Phagocytosis ◽  
Promising Strategy ◽  
Murine Igg1

AbstractOne of the main pathological hallmarks of Alzheimer’s disease (AD) is the intraneuronal accumulation of hyperphosphorylated tau. Passive immunotherapy is a promising strategy for the treatment of AD and there are currently a number of tau-specific monoclonal antibodies in clinical trials. A proposed mechanism of action is to engage and clear extracellular, pathogenic forms of tau. This process has been shown in vitro to be facilitated by microglial phagocytosis through interactions between the antibody-tau complex and microglial Fc-receptors. As this interaction is mediated by the conformation of the antibody's Fc domain, this suggests that the antibody isotype may affect the microglial phagocytosis and clearance of tau, and hence, the overall efficacy of tau antibodies. We therefore aimed to directly compare the efficacy of the tau-specific antibody, RN2N, cloned into a murine IgG1/κ framework, which has low affinity Fc-receptor binding, to that cloned into a murine IgG2a/κ framework, which has high affinity Fc-receptor binding. Our results demonstrate, for RN2N, that although enhanced microglial activation via the IgG2a/κ isotype increased extracellular tau phagocytosis in vitro, the IgG1/κ isoform demonstrated enhanced ability to reduce tau pathology and microgliosis following passive immunisation of the P301L tau transgenic pR5 mouse model.

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