Optical receptors

Another unexpected role of some skeletal pieces has been described. Ophiuroids are a large group of Echinoderms that includes the brittlestars. They have five arms, superficially resembling true starfishes (Asteroidea), and can catch fast motile prey. Aizenberg and coworkers have found that calcite crystals in their skeletons act as optical receptors or lenses. However, it is not known whether the system of lenses and nerves is actually an eye . However, these structures are absent in closely related but not light sensitive species of brittlestars. 

The arrival of the odorant or the odorant/OBP complex at the outer surface of the receptor protein induces a change in the latter. It is not possible to see directly what happens at this point. The receptor must be located in the cell wall and therefore we are dealing with single molecule events and these cannot be studied by techniques such as X-ray crystallography. Similarly, the environment is too complex to be amenable to elucidation by NMR. Therefore, ideas on the exact nature of the initial receptor event are based on calculated guesses extrapolated from what we know about other systems. One popular hypothesis is that the binding sites lie inside the cylindrical channel between the seven trans-membrane helices of the receptor protein. This would be consistent with hormone receptors and with the optical receptors in which the retinal-derived... 

Multi-ion detection by a single optical sensor bearing different binding sites are very interesting in terms of their applications. Because of the versatile derivatiza-tion and conformations of calix[4]arenes, optical receptors for the simultaneous detection of various ions, including cations, anions, and other species, have been developed. 

It is known that molecularly imprinted [3-CD polymer may be used as optical receptor for detection of organic compounds. The molecularly imprinted [3-CD polymer was prepared from [3-CD, using TDI as a crosslinking agent in this procedure A-phenyl-l-naphthylamine (35) served as a template. The molecularly inprinted polymer was fluorometrically characterized using a fibre optic cable attached to a flow-cell. The above sensor was investigated for analytical determination of 35 [82]. 

Substrates involved in molecular recognition may feature a particular shape, size, state of charge, chemical affinity or optical specification (19,30,33—36). In general most of these parameters share. Nevertheless there may be dominating features of a certain substrate molecule to be used by a complementary receptor in the recognition process (9). 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Rochais F, Vilardaga JP, Nikolaev VO et al (2007) Realtime optical recording of Pi-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedi-lol. J Clin Invest 117229-235... 

Figure 22.3 Possible links in the induction of circadian rhythm between daylight, the suprachiasmatic nucleus and melatonin release from the pineal gland. Some fibres in the optic nerve, projecting from the eye to the lateral geniculate nucleus (LGN) in the thalamus, innervate the suprachiasmatic nucleus (SCN) in the anterior hypothalamus, via the retinohypothalamic tract (RHT). Others project to the SCN from the LGN in the geniculohypothalamic tract (GHT). The release of melatonin into the circulation from the pineal gland (PG) is maximal at night and appears to be controlled partly by noradrenaline released from sympathetic nerves originating in the superior cervical ganglion (SCG). Melatonin receptors are found in the SCN, the removal of which dampens melatonin secretion...

HU-210 is (8.1) among the most potent cannabinoids known. Its enantiomer HU-211 (8.2) does not bind to the cannabinoid receptor and lacks psychotropic side effects (as long as optical purity is guaranteed). In animal models it shows analgesic and antiemetic activity. It also shows neuroprotec-tive effects after brain injury and was tested in humans as anti-traiuna agent, where it did not meet the expectations in a clinical phase III trial. 

Drugs most often react with biopolymers called receptors in order to exert their pharmacological effects and the receptors are optically asymmetric and should therefore require a most favorable configuration and conformation for maximal activity. 

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