The Extracellular Domain of the TSH Receptor Has an Immunogenic Epitope Reactive with Graves' IgG but Unrelated to Receptor Function as Well as Determinants Having Different Roles for High Affinity TSH Binding and the Activity of Thyroid-Stimulating Autoantibodies

Thyroid ◽  
1991 ◽  
Vol 1 (4) ◽  
pp. 321-330 ◽  
Author(s):  
SHINJI KOSUGI ◽  
TAKASHI AKAMIZU ◽  
OSAMU TAKAI ◽  
BELLUR S. PRABHAKAR ◽  
LEONARD D. KOHN
Keyword(s):  
Extracellular Domain ◽  
Tsh Receptor ◽  
Receptor Function ◽  
High Affinity ◽  
Immunogenic Epitope

High Affinity Binding of Thyrotropin (TSH) and Thyroid-Stimulating Autoantibody for the TSH Receptor Extracellular Domain

Thyroid ◽  
1994 ◽  
Vol 4 (2) ◽  
pp. 155-159 ◽  
Author(s):  
YUJI NAGAYAMA ◽  
AKIRA TAKESHITA ◽  
WENTIAN LUO ◽  
KIYOTO ASHIZAWA ◽  
NAOKATA YOKOYAMA ◽  
...  
Keyword(s):  
Extracellular Domain ◽  
Tsh Receptor ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity

Anti-TSH receptor antibodies in Graves' disease modulate the kinetic behaviour of autologous thyroid TSH receptors. Evidence of the IgG-induced cross-linkage of autologous TSH receptors

1984 ◽  
Vol 105 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Tjerk W. A. de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Graves Disease ◽  
Kinetic Behaviour ◽  
High Affinity ◽  
Cross Linkage ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors. Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.

Importance of the Extracellular Domain for Prostaglandin EP2 Receptor Function

1999 ◽  
Vol 56 (3) ◽  
pp. 545-551 ◽  
Author(s):  
Brett A. Stillman ◽  
Matthew D. Breyer ◽  
Richard M. Breyer
Keyword(s):  
Extracellular Domain ◽  
Receptor Function ◽  
Ep2 Receptor

scholarly journals trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT2 receptor family

2012 ◽  
Vol 8 ◽  
pp. 1705-1709 ◽  
Author(s):  
Adam Pigott ◽  
Stewart Frescas ◽  
John D McCorvy ◽  
Xi-Ping Huang ◽  
Bryan L Roth ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Side Chain ◽  
Receptor Subtypes ◽  
Receptor Function ◽  
High Affinity ◽  
Receptor Family

A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (−)-(1R,2S)-configuration. Screening for affinity at various serotonin receptor subtypes, however, revealed that the cyclopropane congeners also had increased affinity at several sites in addition to the 5-HT2A and 5-HT2B receptors. Therefore, at appropriate doses – although (−)-4 and (−)-5 may be useful as tools to probe 5-HT2 receptor function – one would need to be mindful that their selectivity for 5-HT2A receptors is somewhat less than for DOI itself.

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