Mammalian receptors

The more than 100-strong family of mammalian receptor tyrosine kinases can be divided into different subfamilies, which are named according to their naturally occurring ligands (Fantl et al., 1993). The subfamilies are classified according to the structure... 

Ozoe Y, Akamatsu M (2001) Non-competitive GABA Antagonists Probing the Mechanisms of Their Selectivity for Insect versus Mammalian Receptors. Pest Manag Sci 57 923... 

Finally, some mammalian receptors (certain NGF and interleukin receptors) are apparently capable of signalling with only one chain. However, in these cases, signalling seems to require the formation of heterodimers with accessory proteins, e.g. co-receptors, or interactions wdth other molecules, such as proteoglycans. Furthermore, there are the insulin receptors, which are constitutive dimers with the monomers covalently linked by... 

Fig. 4.4. A typical surrogate assay for a mammalian receptor in yeast cells.

Other HTS assay advances include the us-e of microorganisms such as bacteria and yeast, the cloning and expression of mammalian receptors in microorganisms, probing protein-protein inlcraclions. and veiy importantly. DNA and protein arrays. These are loo involved to discuss here, but excellent reviews exi.sl.- - The increasing use of HTS to screen fora molecule s absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties has been covered as well. ... 

Nicotine and neonicotinoids are agonists, both of which act at the nicotinic acetylcholine receptor -Na" /K+ ionophore. The structural differences between the insect and mammalian receptors define the selectivity of neonicotinoid toxicity to insects and nicotine toxicity to vertebrates. The proposed concept of the neonicotinoid electronegative pharmacophore... 

Figure 28-3 Classification and basic architecture of cell-surface receptors that couple to G-proteins. Panel A lists the major families and groups of GPCRs.The mammalian receptors are confined to families A, B, and C. Family A is the largest and includes the diverse odorant receptors and prototypic GPCRs, such as rhodopsin and the p-adrenergic receptor. Panel B shows a schematic structure of one of the most extensively characterized GPCRs, the p-adrenergic receptor. Major structural features are indicated and are expanded on in the text, ffrom Conn PM, Melmed. eds.Textbook of endocrinology.Towanta Nj Humana Press 1997.)...

Suzuki YA, Lonnerdal B. Characterization of mammalian receptors for lactoferrin. Biochem Cell Biol 2002 80(l) 75-80. 

R. Neumann It seems to me somehow naive to talk about the insect or the mammalian receptor. I think the movement of companies away from screening houseflies to screening market-relevant insects indicates a widespread belief that target sites and detoxification mechanisms differ widely between insect species. Therefore it is very difficult to relate conclusions about receptor systems in cockroaches, locusts or some other model system to the economic "real world . 

This research is particularly significant to myasthenia gravis (MG, human paralytic syndrome), which is now understood to be a disease in which an autoimmune reaction against nicotinic ACh receptor occurs. In MG these receptors at the neuromuscular junction are being destroyed by specific autoantibodies that cross-link them. More detailed knowledge of the construction of these mammalian receptors is vital to understanding this dread disease. 

Fig. (28). Displacement of [3H]-EBOB from the binding site at rat brain and housefly head GABA receptor-coupled Cl channels. Data were taken from [162]. Open circles Compounds showing low affinity towards both receptors, open triangles compounds with high affinity towards both receptors filled triangles compounds showing medium to high affinity towards the insect and negligible activity towards the mammalian receptor.

Though ryanodine and caffeine show similar potency against insect and mammalian receptors (not shown), differential selectivity is observed for Rynaxypyr . 

Recently, the molecular cloning of 14 different mammalian receptor suhtypes revealed an unexpected heterogeneity within 5-HT receptors. The latest classification of 5-HT receptors takes in account not only their pharmacological profile and their coupling with second messengers hut also their amino add sequence (see figure 1, 2 and ref [1]). 

Debnath and coworkers [153] have demonstrated, in a QSAR study performed using electrotopological state atom indices, that compounds with a [=N-N02] (e.g., 7, 10, 12, 13 and 14), [=CH-N02] (e.g., 8) or [=N-CN]-pharmacophore (e.g., 9 and 11) are more active, selectively, to Drosophila nAChR and safe for humans, whereas N-unsubstituted imines having affinity to mammalian receptor. 

The mode of action of anthranilic diamides has been investigated in detail. It was reported that anthranilic diamides activate RyR, releasing stored calcium from the sarcoendoplasmic reticulum, and exhibit >500-fold differential selectivity toward insect, over mammalian, receptors [32). Anthranilic diamides will be soon classified as RyR modulators within the I RAC classification [2). The two chemical classes, benzenedicarboxamides and anthranilic diamides, could contribute to our understanding of the mechanism of calcium release channels in insects and mammals. 

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