Unknown receptor sites

Salient Features Following are some of the Salient features with regard to the exploration of unknown receptor sites  

The various important and vital aspects of the unknown receptor sites are as given under  

---

A third concept is that phenytoin enhances GABAergic transmission. Chloride ions enhance the binding of phenytoin to a specific but unknown receptor site in the brain. It has been postulated that this binding may enhance GABA-mediated chloride conductance in the postsynaptic membrane. 

The searching for similarity also establishes the exact location(s) of the unknown receptor sites. This may be accomplished judiciously by canying out the investigative studies imder the following two categories ... 

Write a comprehensive essay on the Unknown Receptor Sites with special emphasic upon the following aspects ... 

The contrast between the presence of well defined conformation in secretin and the absence of rigid geometry in bradykinin or CCK pronq>ts the speculation that the cooperative intramolecular interactions which determine the architecture of secretin might be replaced by similar but in-termolecular interactions in CCK (perhaps also in bradykinin), that is by interactions between the hormone and the yet unknown receptor site. Some support for this speculation can be found in the remarkable fact that while with secretin practically the whole chain is needed for full biological activity, this is not true for CCK already relatively short C-terminal sequences reveal the various hormonal activities of the CCK itself. 

Since the body may be viewed as a very complex system of compartments, at first it might appear to be hopeless to try to describe the time course of the drug at the receptor sites in any mathematically rigorous way. The picture is further complicated by the fact that, for many drugs, the locations of the receptor sites are unknown. Fortunately, body compartments are connected by the blood system, and distribution of drugs among the compartments usually occurs much more rapidly than absorption or elimination of the... 

Biochemical site of action Site 1 on voltage-dependent sodium channel Site 5 on voltage-dependent sodium channel Catalytic subunit of phosphorylase phosphatases Kainate receptor in central nervous system Unknown Ciguatoxin site 5 on voltage-dependent sodium channel Maitotoxin calcium channels... 

Anthrax toxin is a bacterial toxin from Bacillus anthracis consisting of three parts protective antigen (PA), lethal factor (LF) and edema factor (EF). Both LF and EF compete for binding sites on the PA protein. The PA protein binds with high affinity to an as yet unknown receptor on macrophages and related cell types. When PA is internalized by the target cells, it functions as a shuttle protein for either EF or LF. Intracellularly, in the acidic environment of the endosome, EF and LF are capable of entering the cytosol by pH-dependent pore formation [139]. 

Mechanism of Action An antihistamine and anticholinergicthat competes for H,-receptor sites on effector cells of the G1 tract, blood vessels, and respiratory tract. The anticholinergic action diminishesvestibular stimulation and depresses labyrinthine function. Therapeutic Effect Prevents symptoms of motion sickness. Pharmacokinetics Well absorbed following PO administration. Metabolized in liver. Excreted in urine. Half-life Unknown. 

Mechanism of Action An anticonvulsant and antineuralgic agent whose exact mechanism is unknown. May increase the synthesis or accumulation of gamma-aminobutyric acid by binding to as-yet-undefined receptor sites in brain tissue. Therapeutic Effect Reduces seizure activity and neuropathic pain. 

Mechanism of Action A tetracyclic compound that blocks reuptake norepi nephri ne by CNS presynaptic neuronal membranes, increasing availability at postsynaptic neuronal receptor sites, and enhances synaptic activity. Therapeutic Effect Produces antidepressant effect, with prominent sedative effects and low anticholinergic activity. Pharmacokinetics Slowly and completely absorbed after PO administration. Protein binding 88%. Metabolized in liver by hydroxylation and oxidative modification. Excreted in urine. Unknown if removed by hemodialysis. Half-life 27-58 hr. 

Completely unknown. Salvia divinorum represents an entirely new class of entheogen. A Novascreen receptor site screening sponsored by David Nichols discovered no binding Inhibition for the forty reference compounds tested, covering all major known receptors. 

Marshall, G.R., Binding-site modeling of unknown receptors. In 3D QSAR in Drug Design, Theory Methods and Applications, Kubinyi, H. (ed.). ESCOM, Leiden, 1993, pp. 80-116. 

Pro-inflammatory cytokines (see p. 432 et seq.) can also induce sleep, the effect depending on the concentration of the cytokine and the time of day. The effect on the sleep profile (increased non-REM and decreased REM sleep) appears to depend on the increased synthesis of prostaglandin D2 and nitric oxide which then alter the circadian rhythm. It is also known that some pro-inflammatory cytokines can affect the reuptake of 5-HT which plays an important role in regulating the sleep-wake profile. The endogenous fatty acid, oleamide, can cause sedation and induce sleep by activating cannabinoid receptors but also by potentiating the action of benzodiazepines on their receptor sites. Whether such action is of physiological relevance is presently unknown. 

Ethylene receptors and regulatory control. The mode of action of ethylene at the molecular level is unknown. Some attempts, however, have been made to determine the receptor sites for ethylene (54) as well as their characteristics (55). There appears to be very little incorporation of ethylene applied to tissues (only about 0.05%). The - - C ethylene incorporated into pea seedling tissues which responded physiologically to the gas was metabolized to C02 and water-soluble metabolites (55). Metabolism of the incorporated ethylene by pea seedlings and other tissues was inhibited by high levels of CO2 (7-10%) and Ag+ ions (10-500 ppm) (56). Ag+ ions prevented the incorporation of ethylene into water-soluble tissue metabolites and... 

Fig. 13.4. Diagrammatic representation of the three-dimensional arrangement of morphine and the analgesic receptor site. The diagrams represent the lower surface of the drug and the upper surface of the receptor complementary surfaces in front of, behind, and in the plane of the paper are represented by—, —, and —, respectively. This drawing is a modified form of the original diagram to take into account the true configuration of morphine, which was unknown in 1954.

---