Receptors regulation

Receptor responses are not static but are regulated by endogenous and exogenous factors. In general, a prolonged increase in the stimulation of various receptors will lead to a decrease in receptor function, and decreased stimulation will lead to an increase in receptor numbers or sensitivity (Fig. 4—6). The mechanisms and significance of these receptor changes are described here. 

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Receptor Regulation and Defects. Specific recognition and the initiation of response are the accepted attributes of the dmg—receptor interaction. However, target cells can alter on both short- and long-term time scales their sensitivity to dmgs. Such regulation, achieved by altering the... 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes... 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

Pregnane X Receptor, Nuclear Receptor Regulation of Drug-metabolizing P450-Enzymes. 

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Second, the time-course of the assays are often of different dimensions depolarizations and ion fluxes are measured in fractions of minutes, while tumor promotion or receptor regulation may take tens of minutes to hours. 

McDonald PH, Chow CW, MiUer WE, Laporte SA, Field ME, Lin FT, Davis RJ, Lefkowitz RJ (2000) Beta-arrestin 2 a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290 1574-1577... 

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Krupnick, J. G. and Benovic, J. L., The role of receptor kinases and arrestins in G-protein-coupled receptor regulation, Annu. Rev. Pharmacol. Toxicol., 38, 289-319, 1998. 

Morisset, S., Rouleau, A., Iigneau, X. el al. (2000). High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 408, 860-4. 

Fredholm, B. B. (1990b). Differential sensitivity to blockade by 4-aminopyridine of presynaptic receptors regulating [3H]acetylcholine release from rat hippocampus. J. Neurochem. 54 (4), 1386-90. 

Huganir, R.L., Delcour, A.H., Greengard, P., Hess, G.P. Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature. 321 774, 1986. 

McGraw DW, Forbes SL, Kramer LA, Liggett SB. Polymorphisms of the 5 leader cistron of the human beta2-adre-nergic receptor regulate receptor expression. J Clin Invest 1998 102 1927-1932. 

Expression of the cloned receptors in Chinese hamster ovary cells, other mammalian cells and Xenopus oocytes has demonstrated differential coupling of these receptors to cellular responses. In general the Mb M3 and M5 receptors regulate phosphoinositide hydrolysis by stimulating PLC. This occurs through selective coupling of the receptor to the pertussis-toxin-insensitive G protein Gq/11,... 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

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