Receptors down-regulation

Srivastava S, Toraldo G, Weitzmann MN, Cenci S, Ross FP, Pacifici R (2001) Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation. J Biol Chem 276 8836-8840... 

Postsynaptic regulation can be considered from two perspectives modulation by the history of activity at the primary receptor (which may up- or down-regulate receptor number or desensitize receptors see Chapter 2) and modulation by other temporally associated events. 

Schroeder, J. T., Bieneman, A. P., Xiao, H. et al. 2005. TLR9- and FceRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression, J Immunol 175 5724-5731. 

People who have built up a drug tolerance often respond to the attenuated effect by increasing the dose administered. As the dose increases, the neurons readjust again by further down-regulating receptors. Consequendy, addicts may not experience a euphoric, psychoactive sensation, but will continue using the drug to avoid uncomfortable feelings associated with a low level of neurotransmitter-receptor interaction. 

Aerosol adniinistration of isoproterenol produces a prompt (2—5 minutes) intense bronchodilatation of relatively short (1 h) duration. The lack of P2-selectivity leads, in many cases, to tachycardia and blood pressure elevation. Also, use of isoproterenol, like all other known P-agonists, results in a down-regulation, or desensitization, of P-adrenergic receptors. This desensitization is only partial, and after time (depending on dose, patient, and agent), a stable, less responsive state is achieved in which P-agonists remain effective. Isoproterenol has been widely used for many years. 

The primary transporter of cholesterol in the blood is low density Hpoprotein (LDL). Once transported intraceUularly, cholesterol homeostasis is controlled primarily by suppressing cholesterol synthesis through inhibition of P-hydroxy-P-methyl gluterate-coenzyme A (HMG—CoA) reductase, acyl CoA—acyl transferase (ACAT), and down-regulation of LDL receptors. An important dmg in the regulation of cholesterol metaboHsm is lovastatin, also known as mevinolin, MK-803, and Mevacor, which is an HMG—CoA reductase inhibitor (Table 5). 

Cagnon, L., and Rossi, J. J. (2000). Down regulation of the CCRS beta-chemokine receptor and inhibition of HIV-1 infection by stable VAl-ribozyme chimeric transcripts. Antisen. Nuc. A. Drug Dev. 10 251—261. 

Adrenergic receptor 2 Amino acid variants appear to be associated with receptor function and agonist induced down regulation. Some variants may predispose to some types of asthma and modulate action of (3-2-adrenergic drugs. 

Trastuzumab (Herceptin) Humanized antibody, IgGi ErbB2/Her-2 Receptor down-regulation Breast cancer... 

Receptor desensitization, internalization, and/or down-regulation may play a role in the development of tolerance to opioid receptor agonists (Clark et al. 

Woody GE, Luborsky L, McLellan AT, et al Psychotherapy for opiate addicts does it help Arch Gen Psychiatry 40 639—645, 1983 Woody GE, McLellan AT, Luborsky L, et al Severity of psychiatric symptoms as a predictor of benefits from psychotherapy the Veterans Administration-Penn study. Am J Psychiatry 141 1172—1177, 1984 Woody GE, McLellan AT, Luborsky L, et al Twelve-month follow-up of psychotherapy for opiate dependence. Am J Psychiatry 144 590-596, 1987 Yabaluri N, Medzihradsky F Down-regulation of mu-opioid receptor by full but not partial agonists is independent of G protein coupling. Mol Pharmacol 52 896-902, 1997... 

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