Simultaneous receptors

This interaction can be of several types If both receptors use a common signal transduction pathway, the activation can result in an additive response by the cell. Conversely, if simultaneous receptor activation triggers opposing signal transduction pathways, the outcome will be an attenuated cellular response. Other types of interactions may include the desensitization or activation of other receptor proteins or second messenger pathways. The final outcome of the activation of multiple signals is an integrated response by the cell. 

Figure 2.21 Schematics of three different types of simultaneous receptors, .e. (a) cascade receptor, e.g. 2.100, (b) ditoptic receptor, e.g. 2.101, and (c) zwitterion receptor, e.g. 2.102.

Cascade receptors represent the earliest simultaneous receptors and some examples date back to the 1970s and 1980s. Typically, more than one metal ion (cation) coordinates to a particular ligand (often a Schiff base or macrocyclic heteroalkane) in a well-defined geometry and the anionic species then coordinates to the metal centre (Figure 2.21(a)) - this complex is known as a casacade... 

Simultaneous receptors exist that can bind neutral and ionic guests. These types of receptors are large macrocycles, such as calixarenes, in which the ion is bound to the functional groups at the lower rim of the calixarene and the neutral (often solvent) molecule is encapsulated within the cavity of fhe bowl, e.g. tetramethoxy-p-f-butylcalix[4]arene (2.116). In the solid state, an Na ion is coordinated to the oxygen atoms of the lower rim of fhe calix[4]arene and the complex contains one molecule of toluene within the hydrophobic cavity (Figure 2.27). 

Moreover, multivariate optimization, the simultaneous optimization of several properties, will increasingly come into focus. A drug should have high selectivity in binding to different receptors and minimal toxicity, good solubility and penetration, and so on. A hair color should have a brilliant shine, be absorbed well, not be washed out, not damage the hair, not be toxic, and be stable under sunlight, etc. 

The macrocychc hexaimine stmcture of Figure 19a forms a homodinuclear cryptate with Cu(I) (122), whereas crown ether boron receptors (Fig. 19b) have been appHed for the simultaneous and selective recognition of complementary cation—anion species such as potassium and fluoride (123) or ammonium and alkoxide ions (124) to yield a heterodinuclear complex (120). 

A persistent idea is that there is a very small number of flavor quaUties or characteristics, called primaries, each detected by a different kind of receptor site in the sensory organ. It is thought that each of these primary sites can be excited independently but that some chemicals can react with more than one site producing the perception of several flavor quaUties simultaneously (12). Sweet, sour, salty, bitter, and umami quaUties are generally accepted as five of the primaries for taste sucrose, hydrochloric acid, sodium chloride, quinine, and glutamate, respectively, are compounds that have these primary tastes. Sucrose is only sweet, quinine is only bitter, etc saccharin, however, is slightly bitter as well as sweet and its Stevens law exponent is 0.8, between that for purely sweet (1.5) and purely bitter (0.6) compounds (34). There is evidence that all compounds with the same primary taste characteristic have the same psychophysical exponent even though they may have different threshold values (24). The flavor of a complex food can be described as a combination of a smaller number of flavor primaries, each with an associated intensity. A flavor may be described as a vector in which the primaries make up the coordinates of the flavor space. 

Nonbenzodiazepine Benzodiazepine Receptor Ligands. The simultaneous discovery of the molecular target for the BZs, the GABA /BZ receptor complex, by two teams of workers (34,35) resulted ia the identification of a number of atypical or anxioselective anxiolytics that, whereas not having the BZ pharmacophore, interacted direcdy with the central BZ receptor. The anxioselective nature of such agents was considered to be... 

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Figure 8. Simultaneous measurement of intracellular Ca and oxidant production in neutrophils. Cells were labeled with Quin-2 and suspended at 2 x lo cells/mL buffer. At time zero, 1 nJf FLPEP was added (upper trace in each panel). In addition, the receptor blocker tBOC was added (3 x 10" M) after 30 s to stop further binding of the stimulus (lower trace in each panel). The excitation wavelength was 3A0 nm. Top panel Quin-2 fluorescence determined on channel B (of Figure 1) using a Corion A90-nm interference filter. The crossover from the superoxide assay has been subtracted. Middle panel Oxidant production (superoxide equivalents) determined by the para-hydroxyphenylacetate assay. Fluorescence was observed at AOO nm (on channel A of Figure 1).

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