Receptor system

Receptor system A system which contaminants enter without inducement. 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

Kenakin, T. P. (1997). Differences between natural and recombinant G-protein coupled receptor systems with varying receptor/G-protein stoichiometry. Trends Pharmacol. Sci. 18 456-464. 

A schematic representation of receptor systems in terms of the cubic ternary complex model is shown in Figure 3.13. The amount of signaling species (as a fraction of total receptor) as defined by the cubic ternary complex model see Section 3.13.8 is expressed as... 

It can be seen from this equation that maximal constitutive activity need not reach a maximal asymptote of unity. Submaximal constitutive activity has been observed with some receptors with maximal receptor expression [28]. While there is scattered evidence that the cubic ternary complex is operative in some receptor systems, and while it is thermodynamically more complete, it also is heuristic... 

Kenakin, T. P. (2000). The pharmacologic consequences of modeling synoptic receptor systems. In Biomedical applications of computer modeling, edited by A. Christopoulos, pp. 1—20. CRC Press, Boca Raton. 

FIGURE 4.15 Complex binding curves for agonists in G-protein unlimited receptor systems. 

Another potential complication can occur if the responsiveness of the receptor system changes temporally. This can happen if the receptor (or host system, or both) demonstrates desensitization (tachyphylaxis) to drug stimulation (see Chapter 2). There are numerous systems where constant stimulation with a drug does not lead to a constant steady-state response. Rather, a fade of the response occurs. This can be due to depletion of a cofactor in the system producing the cellular response or a conformational change in the receptor protein. Such phenomena protect against overactive stimulation of... 

Analyses for Inverse Agonists in Constitntively Active Receptor Systems... 

In constitutively active receptor systems (where the baseline is elevated due to spontaneous formation of receptor active states, see Chapter 3 for full discussion), unless the antagonist has identical affinities for the inactive receptor state, the spontaneously formed active state, and the spontaneously G-protein coupled state (three different receptor conformations, see discussion in Chapter 1 on receptor conformation) it will alter the relative concentrations of these species—and in so doing alter the baseline response. If the antagonist has higher affinity for the... 

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