Binding agonists

The basis of this model is the experimental fact that most agonist dose-response curves are hyperbolic in nature. The reasoning for making this assumption is as follows. If agonist binding is governed by mass action, then the relationship between the agonist-receptor complex and response must either be linear or hyperbolic as well. Response is thus defined as... 

Modulators can be classified as potentiators of effect or antagonists. If potentiation is observed, it is clearly an allosteric effect as orthosteric obfuscation of the agonist binding site cannot lead to potentiation of agonism. 

Heterologous desensitization is a form of desensitization which does not require agonist binding of the receptor. Second messenger dependent kinases such as protein kinase A (PKA) and protein kinase C (PKC) are involved in this form of receptor desensitization. Heterologous desensitization simply depends on the overall kinase activity which is regulated by many different stimuli. 

In the resting (closed) state, the ion channel is occluded by a hydrophobic girdle that constitutes a barrier to ion permeation. Agonist binding in the extracellular domain promotes a conformational change that results in a rotational movement of the M2 helices lining the pore, widening the pore by A. This results... 

SHR Gene map locus cDNA size Natural agonist Binding half-site Main expression... 

Receptors permanently linked to an effector consist of proteins with an extracellular ligand-binding receptor domain and a signal-generating effector domain (Fig. 1). Most of these receptors are composed of two to five structurally related or identical subunits. Effectors can be enzymes or ion channels whose activities are stimulated by agonist binding without significant delay. 

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

Several drugs, the most well-known being local anesthetics and histrionicotoxin (HTX) (28), bind to an allosteric site on the AChR (relative to the agonist binding site). Biochemically, this site is identified by high affinity binding of [ H]Hj2 HTX (Table I). It may be located at the ion channel and coordinates between several of... 

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