Antagonist binding

Two fundamental questions have emerged from these studies, ie, to what extent are agonists and antagonists binding similarly or differendy to the respective receptors, and can inhibitory compounds be developed that are active in vivo in humans as well as in vitro. An oxytocia antagonist that can block premature uterine contractions presents a promising example of the clinical utihty of such stmctures (47). Both linear as well as bicycHc modifications of these hormones also have provided new antagonist stmctures. 

In this histamine H2-receptor model, both histamine and its antagonists bind to [18]aneN6 3 H + forming 1 1 complexes at neutral pH, and the histamine antagonists are more strongly bound to the receptor model (see Fig. 9). Although this picture... 

If the ligand aliosterically affects the affinity of the receptor (antagonist binds to a site separate from that for the tracer ligand) to produce a change in receptor conformation to affect the affinity of the tracer (vide infra) for the tracer ligand (see Chapter 6 for more detail), the displacement curve is given by (see Section 4.6.3)... 

The observation of dependent variable values (in functional experiments this is cellular response) as they happen (i.e., as the agonist or antagonist binds to the receptor and as the cell responds) is referred to as real time. In contrast, a response chosen at a single point in time is referred to as stop-time experimentation. There are certain experimental formats that must utilize stop-time measurement of responses since the preparation is irreparably altered by the process of measuring response. For example, measurement of gene activation through reporter molecules necessitates lysis of the cell. Therefore, only one... 

Parrill AL, Sardar VM, Yuan H (2004) Sphingosine 1-phosphate and lysophosphatidic acid receptors agonist and antagonist binding and progress toward development of receptor-specific ligands. Semin Cell Dev Biol 15 467-476... 

A neutral antagonist binds equally to both active and inactive states of a G-protein-coupled receptor, regardless of activation state, and therefore blocks the actions of agonists and inverse agonists alike. 

If an antagonist binds to the receptor and precludes agonist activation of that receptor by its occupancy, then... 

While the agonist binding domain is thought to be within the transmembrane domains for the monoamine and nucleotide receptors, neuropeptides are thought to bind close to the membrane surface on the extracellular domains of the receptor. It is still not clear whether non-peptide antagonists bind at the same or a different site on the receptor. 

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

Ki Antagonist binding affinity Ki67 Nuclear membrane antigen KLH Keyhole limpet haemocyanin K , Michaelis constant KOS KOS strain of herpes simplex... 

Geary, W.A., II, and Wooten, G.F. Quantitative film autoradiography of opiate agonist and antagonist binding in rat brain. J. Pharmacol Exp Ther 225 234-240, 1983. 

Kourounakis A, Visser C, de Groote M, Ijzerman AP. Differential effects of the allosteric enhancer PD81,723 on agonist and antagonist binding and function at the human wild type and a mutant (T277A) adenosine At receptor. Biochem Pharmacol 2000 61 137-144. 

Dalpiaz A, Townsend-Nicholson A, Beukers MW, Schofield P, Ijzerman AP. Thermodynamics of full agonist, partial agonist and antagonist binding to wild type and mutant adenosine Ai receptors. Biochem Pharmacol 1998 56 1437-1445. 

Arias, H.R. Localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors. Neurochem. Int. 36 595, 2000. 

Receptor Broadly applied to the molecular site of drug action. More specifically, this term describes the plasma membrane proteins to which neurotransmitters, agonists and antagonists bind. 

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