Receptor-mediated mechanisms

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

Chappell DA, Medh JD Receptor-mediated mechanisms of lipoprotein remnant catabolism. Prog Lipid Res 1998 37 393. 

Note CXCL4 may act through CXCR3B or non-receptor-mediated mechanisms. 

Glutamine synthetase, a brain Mn enzyme, is located mainly in astrocytes, and its synthesis may be modulated by nitric oxide (496). Inhibition of this enzyme could be relevant to aging diseases (497). There is evidence that human NT2-N neurons die via ionotropic glutamate receptor-mediated mechanisms when exposed to hypoxia in the presence of glutamate (498). 

In this approach, chimeric peptides [79] are generated as transportable dmg derivatives targeting the receptor-mediated mechanism. Chimeric peptides are formed by hnking a dmg... 

The exact mechanism responsible for the uptake of liposomes by KCs and SECs is not clear. Most studies confirm internalization of whole liposomes in an energy-dependent phagocytic process in which the liposomes are delivered to the lysosomes. The liposomal lipids are completely degraded and the encapsulated solutes released. Neutral liposomes consisting of lipids such as cholesterol and phosphatidylcholine are probably cleared by receptor-mediated mechanisms, due to the adsorption of opsonizing proteins onto the hpid bi-... 

In ERT, intravenously administered enzymes are taken up directly by the affected cells through a receptor-mediated mechanism. 

F. LDL particles, the main carriers of cholesterol in the bloodstream, are taken up into cells by a receptor-mediated mechanism. 

The goal of a drug molecule is to influence cellular function via a receptor-mediated mechanism. Cellular function may be conceptualized into three very broad categories of activity ... 

Because the toxicity of dioxin and dioxin-like compounds is assumed to be elaborated through a common receptor-mediated mechanism, levels greater than 50 ppt TEQs are used to determine whether further site-specific evaluation for dioxins is to occur based on the maximum soil concentrations identified at the site. A level of 1 ppb TEQs is used to determine the potential need for public health actions on a site-specific basis andonthe basis of adequate sampling and measured or projected human exposure—past, present, or future—as determined by the health assessor. 

Similarly to NE, DA also suppresses the firing activity of NE neurons, via the D2-receptor mediated mechanism. NE however has different effects on the firing activity of 5-HT and DA neurons the decrease in the brain NE followed by an increase of activity of DA neurons and by suppression of firing of 5-HT neurons (Guiard et al., 2008). Figure 7 summarizes the reciprocal interactions between NE, 5-HT and DA systems. 

Figure 6. Mechanism of serotonin-induced inhibition of firing activity of norepinephrine neurons. Serotonin increases the GABA and decrease glutamate influx into the locus coeruleus, via 5-HT2A and 5-HT1A receptor-mediated mechanisms, respectively. This increase in GABA and decrease in glutamate influx results in the inhibition of firing activity of norepinephrine neurons. Published with permission of Pierre Blier, M.D., Ph.D., University of Ottawa Institute of Mental Health Research.

Stress-related stimuli probably trigger NE neuronal activity, via the amygdala and PFC afferents. The activation of NE neurons results in an increase in NE transmission in the hypothalamus and limbic system. The increase in NE levels in hypothalamus results in activation of hypothalamus-hypophysis-adrenal (HPA) axis, via a (3-adrenergic receptor-mediated mechanism. An increase in NE in the limbic system stimulates neuronal activity of glutamatergic pyramidal neurons and decreases the firing of GABA basket intemeurons, via a2- and (3-adrenergic mechanisms, respectively. 

The presence of specific receptor-mediated mechanisms such as are common in pesticides. Amount of data available for training sets. 

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