Up regulation, of receptors

Abrupt interruption of propranolol therapy in individuals with angina pectoris has been associated with reappearance of angina, acute myocardial infarction, or death due to a sudden increase in sympathetic nervous system tone to the heart. The mechanisms underlying these reactions are unknown, but they may be the result of an increase in the number of p-receptors that occur following chronic p-adrenoceptor blockade (up-regulation of receptors). When it is advisable to discontinue propranolol administration, such as before coronary bypass surgery, the dosage should be tapered over 2 to 3 days. 

FIGURE 6-2. The neurotransmitter receptor hypothesis of antidepressant action—part 1. Shown here is the monoaminergic neuron in the depressed state, with up regulation of receptors (indicated in the red circle). 

Radtke S, Haan S, Jorissen A, Hermanns HM, et al. 2005. The JAK1 SH2 domain does not fulfill a classical SH2 function in JAK/STAT signaling but plays a role for receptor interaction and up-regulation of receptor surface expression. J Biol Chem. 280 25760-25768. 

Abrupt withdrawal may be less likely to lead to a rebound effect if there is some partial agonist action, since there may be less up-regulation of receptors, such as occurs with prolonged receptor block. 

The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by poly-and monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic. 

Cholestyramine, colestipol, and colesevelam are the bile acidbinding resins or sequestrants (BAS) currently available in the United States. Resins are highly charged molecules that bind to bile adds (which are produced from cholesterol) in the gut. The resin-bile acid complex is then excreted in the feces. The loss of bile causes a compensatory conversion of hepatic cholesterol to bile, reducing hepatocellular stores of cholesterol resulting in an up-regulation of LDL receptors to replenish hepatocellular stores which then result in a decrease in serum cholesterol. Resins have been shown to reduce CHD events in patients without CHD.26... 

D Ambrosio D, Iellem A, Bonecchi R, et al. Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol 1998 161 5111-5115. 

Mori T, Kim J, Yamano T, et al. Epigenetic up-regulation of C-C chemokine receptor 7 and C-X-C chemokine receptor 4 expression in melanoma cells. Cancer Res 2005 65 180-187. 

Forbes et al. saw a slight up-regulation of Connexin 43 in PC-3 cells (androgen unresponsive) with pure lycopene treatment but no Connexin 43 expression (with or without lycopene) in the highly metastatic PC-3MM2 variant (Table 21.2) indicating that with increasing metastatic conversion either the ability to turn on Connexin 43 is lost and/or the receptors responsive to lycopene are lost (Forbes et al. 2003). 

Parker, S.L., Fu, Y., McAllen, K. et al. Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine disproportionate increase of the alpha6 subunit. Mol. Pharmacol. 65 611, 2004. 

Mochizuki, T., Villemagne, V., Scheffel, U. et al. Nicotine induced up-regulation of nicotinic receptors in CD-I mice demonstrated with an in vivo radiotracer gender differences. Synapse. 30 116, 1998. 

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