Down regulation

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. 

Prolonged exposure of -adrenoceptor agonists down-regulates -adrenoceptors, ie, their number decreases and they become less responsive. On the other hand, prolonged exposure to -adrenoceptor antagonists (those without ISA) upregulates -adrenoceptors, ie, their numbers increase and they become more responsive. Therefore, patients on -adrenoceptor blocker therapy should be withdrawn from this medication gradually (40). 

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. 

Kim Y, Yoon JW, Xiao X et al (2007) Selective down-regulation of glioma-associated oncogene 2 inhibits the proliferation of hepatocellular carcinoma cells. Cancer Res 67(8) 35 83-3593... 

Gastric cancer Associated to down regulation of Capn9 gene34... 

CD C14 C14.001 Caspase-1 Potential drug target for down-regulation of the inflammatory mediator, interleukin 1beta, which could ameliorate inflammation and endotoxic shock... 

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... 

Schmidt, J.A. Abdulla, E. (1988). Down regulation of IL-ip biosynthesis by inducers of the heat shock response. J. Itmnunol. 141, 2027—2034. 

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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