Receptor-mediated pathway

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

Secondly, treatment of neutrophils with pertussis toxin, which ADP-ribosylates a neutrophil G protein and causes a loss of cell responsiveness via receptor-mediated pathways (40,41), has minimal effect on the response to HCH (Figure 11, lower panel). Thus it can be concluded that HCH activation of neutrophils is independent of receptor-mediated activation of G proteins. 

WANG TTY, SATHYAMOORTHY N, PHANG J M (1996) Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis. 17 271-5. 

Fig, 2. Regulation of L-type channels by multiple second messenger systems. The cartoon is based on what is known or speculated about how L-type Ca channels might be regulated by proeesses that involve phosphorylation by different receptor mediated pathways. The actual receptors and number of pathways may vary in different cell types. The cartoon is loosely based on events that might occur in a cardiac cell. 

Brown, M. S. and Goldstein, J. L. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science, 232(4746) 34-47. 

Tanaka-Kagawa, T. et al., Arsenite and arsenate activate extracellular signal-regulated kinases 1/2 by an epidermal growth factor receptor-mediated pathway in normal human keratinocytes, Br. J. Dermatol., 149, 1116, 2003. 

Uptake of low-density lipoprotein has been studied479 as a prototype of a receptor-mediated pathway for internalization of external macromolecules. It is a coupled process by which selected, extracellular proteins or peptides are first bound to specific, cell-surface receptors, and then rapidly internalized by the cell. Internalization follows clustering of receptors in specialized regions of the cell surface, called coated pits, that invaginate, to form coated vesicles. 

Fig. 1. Proposed mechanism of action of rituximab associated with the apoptosis pathway. Binding of rituximab with the CD20 antigen up-regulates the production of interleukin-10 (IL-10). The IL-10 autocrine loop down-regulates the expression of the bcl-2 protein, which inhibits the intrinsic pathway (or mitochondrial mediated pathway) of apoptosis. The mitochondrial pathway is induced by intracellular stress signals. The translocation of the bcl-2 protein into the mitochondria leads to the activation of caspase 9 via release of cytochrome c and apoptotic protease-activating factor 1. The other pathway, the extrinsic pathway (or death receptor mediated pathway) activates caspase 8. Subsequently, caspase 8 or 9 activates caspase 3, leading to programmed cell death (apoptosis).

Chen G, Konstantinov AD, Chittim BG, et al. 2001. Synthesis of polybrominated diphenyl ethers and their capacity to induce CYPIA by the Ah receptor mediated pathway. Environ Sci Technol 35(18) 3749-3756. 

A major difference between the inhalational agents and the iv anesthetics is that the former probably exert their biological activity through physical effects while the latter, in most cases, function through a biological receptor-mediated pathway. 

Maher JM, Cheng X, Slitt AL, et al. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 2005 33 956-962. 

Some cell types maintain a low level of caspase 8 in the cytoplasm. Therefore, in the presence of apoptotic stimuli, this small amount of caspase 8 is activated in the DISC complex, and the subsequent activation of effector caspases is not possible. These cell types are called type II and also require the mitochondrial pathway activation. These two pathways can communicate through the cleavage of a Bcl-2 member, Bid, by caspase 8 (Li et al., 1998). Cell lines that have a higher level of caspase 8 in the cytoplasm are called type I. In these cells, Bcl-2 family members do not regulate the death receptor-mediated pathway. 

Cholesterol appears to be taken up from plasma lipoproteins by steroidogenic tissues by two receptor-mediated pathways - the LDL pathway and the HDL pathway. Not all tissues of all species can utilise both of these thus, the LDL pathway appears to occur in all species, including man, whereas the HDL pathway occurs mainly in rodents. LDL lipoproteins interact specifically with cell surface-bound receptors, as shown for, e.g., adrenal [9] and ovary [10], after which internalization occurs by endocytosis and hydrolysis of LDLs, plus their cholesterol ester complement by lysosomal action. 

Internalization of protein hormones is a principal means of hormone degradation in lysosomes through a receptor-mediated pathway [70], There may also be membrane-associated degradative activities for insulin (insulinase) and other protein hormones, however for EGF, degradation occurs exclusively through an intracellular process [68,71]. 

Lee JW, Juliano R. Mitogenic signal transduction hy integrin- and growth factor receptor-mediated pathways. Mol. Cells 2004 17 188-202. 

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