Receptor affinity for

Rational design, 148-149, 152 Real-time assays, 83, 88 Receptor(s). See also Drug receptors affinity for, 6, 63 allosteric model of, 143 Clark s work, 3 classical model of, 44-45 concept of, 2-4 conformations, 13-14, 13 Of conservation equation for, 76 constitutive activity of, 49-51 coupling of, 27 definition of, 2 desensitization of, 34 efficacy for, 6... 

Ironically, SE or TSST-1 concentrations that cause T-cell proliferation do not always correlate with receptor affinity. For instance, SEE binds HLA-DR with 100-fold lower affinity relative to the very similarly structured SEA however, SEE stimulates T-cell proliferation to equivalent levels as SEA. The dose-response curves for cytokine and chemokine production in vitro by staphylococcal superantigen-stimulated cells are also very similar despite differences in affmity/specificity for major histocompatibility complex class II and T-cell receptor V/3 molecules. Overall, these observations suggest that the biological effects of staphylococcal superantigens are induced at rather low, nonsaturating occupancy rates not readily classified by typical biokinetics. 

Jacobs, A.M. and Youngblood, F. Opioid receptor affinity for agonist-antagonist analgesics, J. Am. Paediatr. Med. Assoc. 1992, 82, 520-524. 

It is worth noting that in one pathway toward ternary complex formation, the equilibrium constant Aa represents the receptor affinity for ligand and Aga represents the affinity of ligand-bound receptor for G protein. In this soluble receptor system, there is an opportunity to visualize the alternate pathway directly, where Ag is the receptor affinity for G protein in the absence of ligand, and Aag is the affinity of precoupled receptor (RG) for ligand. 

Guanine Nucleotides Modulation of Receptor Affinity for Agonists... 

Design considerations in the development of effective chimeric peptides include vector specificity for the brain, vector pharmacokinetics, coupling between vector and drag, and intrinsic receptor affinity for the released drug. 

Resistance Resistance is associated with an absence of the receptor protein or a mutation that lowers receptor affinity for the hormone. However, some resistant cells appear to have functional receptors, but some subsequent step(s) is affected. 

Other In vitro studies showed similar receptor affinity for... 

Corticotropin activity can be measured by the increase of corticosterone in venous blood of hypophysec-tomized or dexamethasone-blocked rats, as a singledose test when receptor affinity for ACTH receptor is found with a test compound. The test can be used to measure time-response curves of corticotropin preparations, and compounds with a adrenal stimulating activity (Vogel 1969a,b). The use of hypophysec-tomized rats for evaluation of the pituitary response... 

Terfenadine binds to peripheral H-1 receptors. Receptor affinity for muscarinic, a, and /i-adrenergic receptors is low. Poor penetration of terfenadine across the blood-brain barrier limits central nervous system effects. Therefore, terfenadine is classified as nonsedating and lacks anticholinergic side effects. However, accumulation of the parent drug, terfenadine, results in prolongation of the QT interval by blocking the delayed rectifier potassium current in the heart. Prolongation of the QT interval can lead to torsade de pointes and death. 

Prior to cloning of the opioid receptors, affinity for these receptors was most commonly determined by the use of homogenates or membrane fractions from rat, guinea pig, or mouse brain, which contain all three types of opioid receptors. The relative amounts of different opioid receptor types vary between species, however, particularly for k receptors. In rat brain k opioid receptors constitute only about 10-15% of the total number of opioid receptor sites (124), whereas in species such as guinea pig they represent approximately 30% of the total opioid receptor population (125). Over 80% of the opioid receptors in the guinea pig cerebellum are k receptors (126), so this tissue was frequently used in K-receptor bind-... 

Schematic representation of glucose (or galactose) transport by the enterocyte. Glucose binds to the receptor, facilitated by the simultaneous binding of two Na+ at separate sites. The glucose and Na" " are released in the cytosol as the receptor affinity for them decreases. The Na" " are actively extruded at the basolateral surface into the intercellular space by Na+,K+-ATPase, which provides the energy for the overall transport. Glucose is transported out of the cell into the intercellular space and thence to portal capillaries, both by a serosal carrier and by diffusion. (Reproduced with permission from G. M. Gray, Carbohydrate Absorption and Malabsorption in Gastrointestinal Physiology. Raven Press,...

Oprea, T.I., Kurunczi, L., Olah, M. and Simon, Z. (2001) MTD-PLS a PLS-based variant of the MTD method. A 3D-QSAR analysis of receptor affinities for a series of halogenated dibenzoxin and biphenyl derivatives. SAR S( QSAR Environ. Res., 12, 75-92. 

Perez Gonzalez, M., Suarez, P.L., Fall, Y. and Gomez, G. (2005) Quantitative structure-activity relationship studies of vitamin D receptor affinity for analogues of la,25-dihydroxyvitamin Dj. 1. WHIM descriptors. Bioorg. Med. Chem. Lett., 15, 5165-5169. 

To determine receptor affinity for cAMP in phosphate buffer, follow steps 1-4 of Subheading 3.2. 

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