Receptor Presentation

A systematic nomenclature for nAChRs has yet to evolve. An N nomenclature describes receptors present ia muscle as N. These are activated by phenyltrimethylammonium (PTMA) (15) and blocked by t5 -tubocurariae (16) and a-bungarotoxiu (a-BgT) (17). N2 receptors are present ia ganglia and are activated by l,l-dimethyl-4-phenylpipera2inium (DMPP) (18) and blocked by trimethaphan (19) and bis-quatemary agents, with hexamethonium (20) being the most potent. 

The term endocrine disrupter (ED) has tended to be used for those chemicals which act specifically at the level of the hormone receptor present in the target cells of various organs. Such chemicals may either mimic the action of the natural hormone (agonistic activity) or are sufficiently similar in molecular shape to the naturally produced hormone to interfere with the interaction between the hormone and receptor, thus blocking or impeding the activation of the receptor (antagonsitic activity). Such effects may occur at very low concentrations (as with the endogenous hormone), compared with the concentrations normally required to elicit the more traditional toxic effects attributed to chemicals. Recently,... 

Langer, SZ (1997) 25 years since the discovery of pres5maptic receptors present knowledge and future perspectives. Trends Pharmacol. Sci. 18 95-99. 

Since receptors are embedded in cell membranes it is more convenient to consider the amount of receptor either free or bound as a proportion of the total receptor present. The proportion of receptors in state R (free) is... 

The first is glycosaminoglycan, a compound produced by the body that coats the epithelial cells of the bladder. This compound essentially separates the bladder from the urine by forming a protective layer against bacterial adhesion.14 A second compound known as Tamm-Horsfall protein is secreted into the urine, and prevents E. coli from binding to receptors present on the surface of the bladder. Other factors implicated in contributing to host defense mechanisms include immunoglobulins, specifically IgA, and lactobacilli, bacteria that are part of the normal vaginal flora.13,15... 

Alemtuzumab is the antibody to the CD52 receptor present on B and T lymphocytes. The pharmacokinetics of alemtuzumab demonstrate a terminal half-life of 7 days. Alemtuzumab has shown clinical activity in the treatment of chronic lymphocytic leukemia. Severe and prolonged (6 months) immunosuppression may result, which necessitates prophylaxis with cotrimox-azole and antivirals to prevent opportunistic infections. 

This hot antibody is linked to radioactive iodine and binds to the CD20 receptor present on B lymphocytes (see Rituximab above). Tositumomab has shown activity in non-Hodgkin s lymphoma. Hematologic toxicity occurs several weeks after administration and may persist for months. Since radioactive iodine may have adverse effects on the thyroid, all patients must receive thyroid-blocking agents. 

The CB1 receptors present in the hippocampus, amygdala, and cerebral cortex may be responsible for observations that cannabimimetics are effective against some types of seizures (Consroe, 1998). The anticonvulsant and antispastic effects of cannabinoids are well documented, however the mechanisms of these effects are still unclear (Nahas, 1999). 

Phase-shifting by melatonin is attributed to its action at MT2 receptors present in the SCN (Liu et al. 1997). The chronobiological effect of melatonin is due to its direct influence on the electrical and metabolic activity of the SCN, a finding that has been confirmed both in vivo and in vitro. The application of melatonin directly to the SCN significantly increases the amplitude of the melatonin peak, thereby suggesting that in addition to its phase-shifting effect melatonin directly acts on the amplitude of the oscillations (Pevet et al. 2002). However, this amplitude modulation seems to be unrelated to clock gene expression in the SCN (Poirel et al. 2003). 

Fig. 21.3. Two-micropipette current-clamp recording and effect of maintained application of 30 pM levamisole, which produces a 15 mV depolarization (upward movement of trace). The downward transients are the result of injected current pulses used to measure membrane conductance. The trace gets narrower as the input conductance increases from 2.35 pS to 4.35 pS as the levamisole ion channels open. The peak amplitude of the membrane potential response and change in input conductance are used as an assay of the number and activity of the levamisole ion channel receptors present in the muscle cell membrane. The response was fully reversible on washing (not shown).

Fig. 5 Proposed signal transduction mechanisms that stimulate the pheromone biosynthetic pathway in Helicoverpa zea and Bombyx mori. It is proposed that PBAN binds to a G protein-coupled receptor present in the cell membrane that upon PBAN binding will induce a receptor-activated calcium channel to open causing an influx of extracellular calcium. This calcium binds to calmodulin and in the case of B. mori will directly stimulate a phosphatase that will dephosphorylate and activate a reductase in the biosynthetic pathway. In H. zea the calcium-calmodulin will activate adenylate cyclase to produce cAMP that will then act through kinases and/or phosphatases to stimulate acetyl-CoA carboxylase in the biosynthetic pathway...

Scatchard analysis is very useful in certain therapeutic situations. For example, this type of analysis is used to determine the number of estrogen receptors present in a biopsy of breast tissue prior to developing a drug treatment regimen for breast cancer in a patient. 

No one interferon will display all of these biological activities. Effects are initiated by the binding of the interferon to its specific cell surface receptor present in the plasma membrane of sensitive cells. IFN-a and -P display significant amino acid sequence homology (30 per cent), bind to the same receptor, induce similar biological activities and are acid stable. For these reasons, IFN-a and IFN-P are sometimes collectively referred to as type I interferons, or acid-stable interferons. 

The IL-ls induce their characteristic biological activities by binding to specific cell surface receptors present on sensitive cells. Two distinct receptors, type I and II, have been identified. Both IL-la and IL-ip can bind both receptors. The type I receptor is an 80 kDa transmembrane glycoprotein. It is a member of the IgG superfamily. This receptor is expressed predominantly on fibroblasts, keratinocytes, hepatocytes and endothelial cells. The type II receptor is a 60 kDa transmembrane glycoprotein, expressed mainly on B-lymphocytes, bone marrow cells and polymorphonuclear leukocytes. It displays a very short (29 amino acid) intracellular domain,... 

TABLE 13-2 Serotonin receptors present in the central nervous system. 

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