Receptors chemical nature

Chin CN, Lucas-Lenard J, Abadji V, Kendall DA. Ligand binding and modulation of cyclic AMP levels depend on the chemical nature of residue 192 of the human cannabinoid receptor 1. J Neurochem 1998 70 366-373. 

Many microorganisms, when in iron-depleted conditions, are able to mobilize environmental iron by secreting low-molecular weight, high-affinity ironchelating compounds called siderophores, as well as cell-surface receptors for the ferric-siderophore complex and other proteins necessary for their uptake. Over the last three decades we have learned a lot about the chemical nature of these... 

As previously noted, the LBD of the receptor presents a series of functions that are not very well delimited such as those of dimerization with another receptor, nuclear translocation, and activation of the ligand-dependent gene transcription. As was just mentioned, the interaction of a ligand with its receptor has as its immediate consequence the conformational change of the molecule, a change that also determines the molecule s functionality. The importance of this point is that the stated conformational change is predetermined by the chemical nature of the ligand and the form in which it interacts with the receptor. 

As the chemical models mentioned here refer to some fundamental thermochemical and electronic effects of molecules, their application is not restricted to the prediction of chemical reactivity data. In fact, in the development of the models extensive comparisons were made with physical data, and thus such data can also be predicted from our models. Furthermore, some of the mechanisms responsible for binding substrates to receptors are naturally enough founded on quite similar electronic effects to those responsible for chemical reactivity. This suggest the use of the models developed here to calculate parameters for quantitative structure-activity relationships (QSAR). 

This experiment represents a scenario when an organic lead compound is available. We chose morphine, a known opiate receptor ligand of non-peptide chemical nature, as a hypothetical lead compound. The averaged frequency distribution based on all four SA runs is obtained (data not shown). The most frequent building block was Dll. Building blocks DIO, D12, D14, and 03 were less frequent, but all above random expectation. 

The local anesthetics can be broadly categorized on the basis of the chemical nature of the linkage contained within the intermediate alkyl chain group. The amide local anesthetics include lidocaine (7.5), mepivacaine (7.6), bupivacaine (7.7), etidocaine (7.8), prilocaine (7.9), and ropivacaine (7.10) the ester local anesthetics include cocaine (7.11), procaine (7.12), benzocaine (7.13), and tetracaine (7.14). Since the pharmacodynamic interaction of both amide and ester local anesthetics with the same Na" channel receptor is essentially idenhcal, the amide and ester functional groups are bioisosterically equivalent. However, amide and ester local anesthetics are not equal from a pharmacokinetic perspective. Since ester links are more susceptible to hydrolysis than amide links. 

Hormones are usually produced by specialized cells and initiate a reaction in only a certain cell type. Only those cells that possess a cognate protein, the receptor of the hormone, can act as target cells. Receptors specifically recognize and bind the cognate hormone based on their chemical nature. The binding of the hormone to the receptor in the target cell induces an intracellular cascade of reactions at whose end lies a defined biochemical response. The pathway from receptor bound signaling molecule to final biochemical response is complex and occurs under the participation of many proteins. 

Anandamide was isolated from water-insoluble fractions of the porcine brain. It binds to CB1 with rather moderate affinity (Ki 61 nM) and a low affinity for the CB2 receptor (Ki 1930 nM). The name anandamide is based on its chemical nature (an amide) and the Sanskrit word ananda meaning bliss. The chemical structure of anandamide can be divided into two major molecular fragments a polar ethanolamido head group and a hydrophobic arachidonyl chain. The polar head group comprises a secondary amide functionality with an N-hydroxyalkyl substituent while the lipophilic fragment is a non-conjugated c/ s tetraolefinic chain and an n-pentyl chain reminiscent of the lipophilic side chain found in the classical cannabinoids. A number of anandamide analogs have been synthesized and demonstrated to have considerable selectivity for the CB1 receptor in comparison to the CB2 receptor. 

The function of a receptor depends on its high specihcity for particular ligands. This often involves the stereochemical ht between a ligand and a receptor, the idea of a lock and key, similar to the interaction of enzymes with various substrates. It should be noted, however, that toxicant-receptor interactions are often around 100 times as strong as enzyme-substrate interactions. Furthermore, whereas an enzyme generally alters a substrate chemically (such as by hydrolysis), a toxicant does not usually change the chemical nature of a receptor other than binding to it. In... 

Several lines of evidence indicate that macromolecules of as yet unidentified chemical nature, produced by cancers and released into the systemic circulation, are responsible for the biochemical alterations in the liver and other host organs. In view of the diverse regulatory properties of the many different enzymes that increase or decrease towards their immature level (see Table III), a deficiency or excess in any given endocrine or dietary factor can clearly not explain the phenomenon. Nor has it been possible to implicate reductions in the efficacy of these factors. Subnormal concentration of the nuclear thyroid hormone receptor has been noted in the liver of tumor-bearing animals(24) however, since losses in the T3-inducible catalysts of the same liver occurred at much earlier stages of tumor-bearing,(24) the subnormal receptor concentration could clearly not be the cause of these losses but was probably another, and rather late, reflection of the process of biochemical undifferentiation. 

Search receptor database for the classification of receptors according to the chemical nature of their ligands. 

Spelsberg and colleagues recently reported the production of monoclonal antibodies against acceptor proteins isolated from hen oviduct [120]. The antibodies inhibit the binding of PR to nuclear acceptor sites in a cell free system and they appear to bind directly to acceptor proteins and not to DNA or receptors. These antibodies will be used to isolate and identify specific acceptor proteins and to further characterize their biological and chemical nature. 

During the past several years ideas regarding the nature of opioid receptors have evolved rapidly. Multiple receptor hypotheses gained favor and a number of discrete receptor types have been characterized. This increasingly complex area has been covered in Chapters 10 and 13. So far we have no evidence for the chemical nature of opioid receptors or for whether differences between receptor types are gross or relatively small. 

The Chemical Nature of the Receptor Site. International Review ofNeuro-... 

The cellular interaction of agonists depends on the physico-chemical nature and on the topographical distribution of the membrane receptors (62). Thus thrombin and PGE, mediated responses would depend on the number and the type (high affinity/low affinity) of receptors available for interaction with thrombin or PGE, respectively. The possibility diat platelets fiwrn SHR exhibit greater sensitivity to thrombin and PGE, because of differences in munber or affinity of their respective receptors has been examined by us (23,24). Hirombin as well as PGE, binding sites/platelets and dissociation constants have been found to be similar in WKY and SHR platelets (Fig.7, ref 23,24). Therefore, increased platelet reactivity to thrombin or PGE, is not attributable to changes in the number or the affinity of their respective receptors. 

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