Receptor identification

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

Prioleau, C., Visiers, I., Ebersole, B. J., Weinstein, H., and Sealfon, S. (2002) Conserved helix7 tyrosine acts as a multistate conformational switch in the 5-HT2C receptor Identification of a novel locked-on phenotype and double revertant mutations. J. Biol. Chem. 277, 36577-36584. 

Geva, A., Lassere, T. B., Lichtarge, O., Pollitt, S. K., and Baranski, T. J. (2000) Genetic mapping of the human C5a receptor. Identification of transmembrane amino acids critical for receptor function. J. Biol. Chem. 275, 35393-35401. 

Wang CD, Buck MA, Fraser CM (1991) Site-directed mutagenesis of a2A-adrenergic receptors identification of amino acids involved in iigand binding and receptor activation by agonists. Mol Pharmacol 40,168-179... 

Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R. Evaluation of histamine HI-, H2-, and H3-receptor ligands at the human histamine H4 receptor identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther 2005 314 1310-21. 

When one starts to work with a new class of molecules or a new tissue, it is important to use an extensive set of criteria for receptor identification in both in vitro and in vivo smdies. These criteria are as follows ... 

R. Schorr, R. J. Defkowitz, M. G. Caron (1981). Purification of the P-adrenergic receptor identification of the hormone binding subunit. J. Biol Chem. 256 5820-5826. 

Wang CD, Gallaher TK, Shih JC. Site-directed mutagenesis of the serotonin 5-hydroxytrypamine2 receptor identification of amino acids necessary for ligand binding and receptor activation. Mol Pharmacol 1993 43 931-940. 

Burstein ES, Ma J, Wong S, Gao Y, Pham E, et al. 2005. Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors Identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther 15 1272-1278. 

Wo, Z. G., and Oswald, R. E. (1996). Ligand binding characteristics and related structural features of goldfish kainate receptors Identification of a conserved disulfide bond and three residues important for ligand binding. Mol. Pharmacol. 50, 770-780. 

Kuhse, J., Laube, B., Magalei, D., Betz, H. (1993). Assembly of the inhibitory glycine receptor identification of amino acid sequence motifs governing subunit stoichiometry. Neuron 11 1049-56. 

Phalipou, S., Seyer, R., Cotte, N., Brenton, C., Barberis, C., Hibert, M., Mouillac, B. Docking of linear peptide antagonists into the human Via vasopressin receptor Identification of binding domains by photoaffinity labelling. J. Biol Chem., 1999, 274, 23316-23327. 

Williams LT, Lefkowitz RJ. a-Adrenergic receptor identification by [3H]dihydro-ergocryptine binding. Science 1976 192 791-793. 

Fraser CM. Site-directed mutagenesis of P-adrenergic receptors—identification of conserved cysteine residues that independently affect ligand-binding and receptor activation. J Biol Chem 1989 264 9266-9270. 

Etzel JP, Rana BK, Wen G, et al. Genetic analysis of the human a2B-adrcncrgic receptor identification of a particular genotype as a possible cardiovascular risk factor. Unpublished manuscript. 

Dominguez, C., Prieto, L., Valli, M. J., et al. (2005) Methyl substitution of 2-aminobicyclo[3.1. Ojhexane 2,6-dicarboxylate (LY354740) determines functional activity at metabotropic glutamate receptors identification of a subtype selective mGlu2 receptor agonist. Journal of Medicinal Chemistry, 48, 3605-3612. 

Le Goff, P., Montano, M.M., Schodin, D.J. and Katzenellenbogen, B.S. (1994) Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. The Journal of Biological Chemistry, 269, 4458-4466. 

Raynor K, Murphy W, Coy D, Taylor J, Moreau J-P, Yasuda K, Bell GI, Reisine T (1993b) Cloned somatostatin receptors identification of subtype selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol 43 838-844 Reichlin S (1983) Somatostatin. In Krieger DT, Brownstein MJ, Martin JB (eds) Brain peptides. Wiley, New York, pp 711-752... 

M. McPherson, Y. Yang, P.W. Hammond, B.L. Kreider, Drug receptor identification from multiple tissues using cellular-derived mRNA display libraries, Chem. Biol. 2002,... 

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