Multiple-site receptors

TABLE 10.2 Responses of multiple-site receptors to various binding plots... 

The opioid peptides vary in their binding affinities for the multiple opioid receptor types. Leu- and Met-enkephalin have a higher affinity for 5-receptors than for the other opioid receptor types (68), whereas the dynorphin peptides have a higher affinity for K-sites (69). P-Endorphin binds with equal affinity to both p- and 5-receptors, but binds with lower affinity to K-sites (70). The existence of a P-endorphin-selective receptor, the S-receptor, has been postulated whether this site is actually a separate P-endorphin-selective receptor or is a subtype of a classical opioid receptor is a matter of controversy (71,72). The existence of opioid receptor subtypes in general is quite controversial although there is some evidence for subtypes of p- (73), 5-(74), and K-receptors (72,75), confirmation of which may be obtained by future molecular cloning studies. 

Zukin, R.S., and Zukin, S.R. Demonstration of 3H-cyclazocine binding to multiple opiate receptor sites. Mol Pharmacol 20 246-254, 1981a. 

Heidmann, T. Oswald, R.E. and Changeux, J.-P. Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments from Torpedo marmorata. Biochemistry 22 3112-3127, 1983. 

Nicotine affects nearly every physiological system of the body (Le Houezec and Benowitz 1991). However, the effects are complex and unpredictable due to actions on multiple sites, and the stimulation-desensitization of nicotinic receptors. 

Lee, S. P., O Dowd, B. F., Rajaram, R. D., Nguyen, T., and George, S. R. (2003) D2 dopamine receptor homodimeiization is mediated by multiple sites of interaction, including an intermo-lecular interaction involving transmembrane domain 4. Biochemistry. 42, 11023-11031. 

Figure 12.16 Multiple sites of hormone effects on the same biochemical process. The hormone binds to its receptor activating the effector system which increases the activity of two separate reactions in the same biochemical pathway (process) to increase flux through the pathway. This means that the flux can change without large changes in the concentrations of intermediates in the pathway, i.e. activation of E and E4 ensures increased flux from S to the product P with little change in the concentrab ons of A, B or C.

Majewska MD, Demirgoren S, Spivak CE, et al Binding of pregenenolone sulfate to rat brain membranes suggests multiple sites of steroid action at the GABAa receptor. Fur J Pharmacol Mol Pharmacol 189 307-315, 1990 Malenka RC, Kauer JA, Perkel DJ, et al The impact of postsynaptic calcium on synaptic transmission—its role in long-term potentiation. Trends Neurosci 12 444-450, 1989... 

Wood, P.L. Multiple opiate receptors support for unique mu, delta and kappa sites, Neuropharmacology 1982, 21, 487-497. 

In addition to the multiplicity of receptor sites for glutamate, the NMDA receptors bear their own complexity as they are constructed as multimers from three distinguishable subunit classes (i.e. NR1, NR2 and NR3 subunit class). With regard to the stoichiometry of the NMDA receptor there is still some debate as to whether a native NMDA-gated ion channel within the cell membrane consists of either a tetramer or pentamer. More recently, it has been suggested that the tetramic stoichiometry is more probable (Laube et al., 1998 Hollmann, 1999). 

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