Receptor interactions with

Fig. 10. The receptor—G-protein sequence. An activated receptor interacts with the trimeric GDP-ligated receptor to cause an interchange of GDP by GTP and dissociation into the activated Ga—GTP (left) and G y (right) subunits. These then interact with a variety of effectors. The purpose of the activated...

Figure 9.17 Imagine that a left hand interacts with a chiral object, much as a biological receptor interacts with a chiral molecule, (a) One enantiomer fits into the hand perfectly green thumb, red palm, and gray pinkie finger, with the blue substituent exposed. (b The other enantiomer, however, can t fit into the hand. When the green thumb and gray pinkie finger interact appropriately, the palm holds a blue substituent rather than a red one, with the red substituent exposed.

In this way, although ERs participate in all cases and in all cells capable of responding to estrogens, the nature and intensity of the response is conditioned by the receptor interaction with three different types of molecules estrogen (steroid or not), DNA (through the HRE sequences), and the protein-protein interactions, including cofactors of transcription as well as elements of the signaling pathway from membrane receptors. 

Klinge CM (2001) Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res 29 2905... 

When the receptor interacts with its associated G protein, the conformation of the guanine-nucleotide-binding site is altered. The subunits then dissociate, and a phosphatidylinositol-specific phospholipase C (PI-PLC) is activated [5]. The subsequent hydrolysis of phosphatidylinositol bisphosphate then produces inositol triphosphate (IP3) and diacylglycerol (DAG), which are known to be secondary messengers. For example, the water soluble IP3 is released into the cell where its ultimate targets are the calcium storage organelles from which Ca2+ is released [3]. The presence of DAG in cells is known to activate the cellular enzyme protein kinase C (PKC) [6, 7], which phosphorylates a number of cellular... 

Puga, A., et. al., Aromatic hydrocarbon receptor interaction with the retinoblastoma protein potentiates repression of E2F-dependent transcription and cell cycle arrest, J. Biol. Chem., 275, 2943, 2000. 

Karpa, K. D., Lin, R., Kabbani, N., and Levenson, R. (2000) The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf D3-D3nf interaction causes mislocalization of D3 receptors. Mol. Pharmacol. 58,677-683. 

Pratt WB, Toft DO. (1997) Steroid receptor interactions with heat shock protein and immu-nophilin chaperones. Endocr Rev. 18, 306-360. 

Receptors fall into two general classes. Many are proteins embedded in biological membranes. These proteins nsually span the membrane. The extracellular domain of the receptor interacts with the signaling molecule, changing the structure of the receptor in a way that transmits the information that a signal has arrived to an intracellnlar domain, which then acts to alter some aspect of cellular metabolism. 

Sklar, L. A. and Finney, D. A. (1982) Analysis of ligand-receptor interactions with the fluorescence activated cell sorter. Cytometry 3,161-165. 

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

STPs (2). Class 1 cytokine receptors interact with three different STPs (gpl30. Pc. and Yc). The STPs themselves do not bind cytokines, but conduct the signal to tyrosine kinases (3). The fact that different cytokines can activate the same STP via their receptors explains the overlapping biological activity of some cytokines. 

Murphy, D.L., Andrews, A.M., Wichems, C.H., Li, Q., Tohda, M., and Greenberg, B. (1998) Brain serotonin neurotransmission an overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. J Clin Psychiatry 59 5uppl 15 4-12. 

Regrettably, the receptor classification system is much more complex than this. For example, the chemokine class of cytokine receptors is further subdivided into at least 16-20 different receptor subtypes, including CCRl, CCR2. .. CCRll, CXCRl, CXCR2. .. CXCR5. These receptors interact with more than 25-30 different types of chemokines. 

Fig. 12. A pictorial representation of adenylate cyclase and hormone receptors interacting with a membrane. The GTP control component is also shown. The different hormone receptors may not interact directly with the adenylate cyclase and may be diffusing freely in the membrane until a hormone is bound.

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