Receptor binding, enhancement

Creese I, Burt DR, Snyder SH (1977) Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197 596-598. 

Lycke NY. Cholera toxin promotes B-cell isotype switching by two dififerent mechanisms. cAMP induction augments germ-line H-chain RNA transcripts whereas membrane ganglioside GMl-receptor binding enhances later events in differentiation. J Immunol 1993 150(11) 4810-4821. 

J) At position 1, an acidic side chain two or three carbons long should be present. The natural L-alanyl side chain reduces receptor binding but enhances in vivo activity by increasing access to the receptor and by retarding metaboHsm and excretion. The enantiomeric D-analogues retain considerable activity in contrast to other bioactive substances (17). 

Bruns RF, Fergus JH. Allosteric enhancement of adenosine Ai receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharmacol 1990 38 939-949. 

Lipophilicity is an important consideration in the design of biologically active compounds because it often controls absorption, transport, or receptor binding that is, it is a property that can enhance the bioavailability of a compound. The presence of fluorine in a substituent gives rise to enhanced lipophilicity. 

Because the chemical structure of a molecule encodes its biological properties, structure has long served as the primary variable and determinant for the discovery of new drugs by medicinal chemists. For this reason, systematic structural modification has been the primary tool of choice to isolate and enhance a desired biologic activity. Moreover, with the relatively recent development of in vitro receptor-binding assays, combinatorial methods of chemical synthesis, and computer graphics, the overall approach to structural modification has become increasingly sophisticated. 

The polymers used for fluorescence detection discussed thus far have all used either a synthetically linked polymer as the signal transducer for enhanced detection or some type of hybridization of the polymer with a receptor for ligand-receptor binding signaling. One of the most notable aspects of CPs is their ability to act as direct reporters for the detection of small molecules, or for conformational changes and protein aggregates. 

Integrin receptor-binding peptides have been used to enhance liposome binding, uptake, and expression (25,47 9). The inclusion of an 0(5pi integrin-targeted peptide into a liposomal complex enhanced transfection efficiency four- to five-fold in Jurkat cells and 10- to 13-fold in TF-1 cells (48). Confocal and electron microscopy revealed that the mechanism of cell entry conferred by RGD peptides on liposomes is predominantly by clathrin-coated endocytosis rather than by phagocytosis (50). 

Boonyaratanakornkit, V., Melvin, V., Prendergast, P., Altmann, M., Ronfani, L., Bianchi, M.E., Taraseviciene, L., Nordeen, S.K., Allegretto, E.A., and Edwards, D.P. (1998) High-mobility group chromatin proteins 1 and 2 functionally interact with steroid hormone receptors to enhance their DNA binding in vitro and transcriptional activity in mammalian cells. Mol. Cell. Biol. 18, 4471 487. 

Arnsten AFT, Leslie FM (1991) Behavioural and receptor binding analysis of the Oj-agonist, UK-14304 (5 bromo-6 (2-imidazoline-2-yl amino) quinoxaline) evidence for cognitive enhancement at an a -adrenoceptor subtype. Neuropharmacology 30 1279-1289... 

Mechanism of Action Abarbiturate that binds at the GABA receptor complex, enhancing GABA activity. Therapeutic Effect Depresses central nervous system (CNS) activity and reticular activating system. 

To date, little postmortem work has been done in human cannabis abusers. Preclinical studies indicate that chronic treatment with 5 -THC markedly reduces CBj receptor binding in all brain areas containing this receptor (cerebellum, hippocampus, cortex, globus pal-lidus, striatum), and enhances the cAMP pathway (Rubino et ah, 2000). Other preclinical work has shown that the cannabinoid receptor reserve is larger than that for most other G protein-coupled receptor systems (Gifford et ah, 1999). This means that at occupancies as low as 0.13%, 50% of maximal inhibition of Ach release is achieved. 

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