Neurotransmitters binding sites

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Key Words Serotonin3 receptor 5-hydroxytryptamine3 receptor Cys-loop receptor ligand-gated ion channel ionotropic receptor neurotransmitter binding site. 

These areas may not be used by the natural neurotransmitter, but they can be used by other molecules. If these molecules bind to such areas and happen to lie over or partially lie over the neurotransmitter binding site, then they will act as antagonists... 

Figure 4 Schematic representation of predicted neurotransmitter binding sites A dopamine B adrenaline C acetylcholine D serotonin. Helix axes are represented as vertical lines and numbered 1 to 7. Residues surrounding the neurotransmitter are schematically displayed and numbered in a coded manner the first digit indicates the transmembrane domain an the next two digits correspond to the rank of the residue in this domain (reproduced with the authorisation of the authors and publishers, from Medecine/Science 1993, 9, 31-40.).

We have already seen, in Section 5.4 on cluster analysis, the application of this method to a set of multiple response data (Fig. 5.9). In this example the biological data consisted of 12 different in vivo assays in rats so the y (dependent) variable was a 40 (compounds) by 12 matrix. These compounds exert their pharmacological effects by binding to one or more of the neurotransmitter binding sites in the brain. Such binding may be characterized by in vitro binding experiments carried out on isolated... 

G-protein-coupled Receptors. Figure 2 Diagram illustrating the binding sites for different families of hormones and neurotransmitters on their receptors. 

Synaptic vesicles mediate the release of small molecules other than classical neurotransmitters and neuropeptides. Of these, zinc and ATP are the best characterized. NMDA and GABA receptors contain binding sites for zinc, and zinc exerts a direct effect on... 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

DERIVATION OF THE HILL COEFFICIENT (OR SLOPE) AS A DETERMINANT OF THE NUMBER OF BINDING SITES FOR AN AGONIST (NEUROTRANSMITTER) ON ITS RECEPTOR... 

Additional studies in rats in vivo and in rat tissues or cells in vitro have focused on potential relationships between the effects of lead on neurotransmitter systems and neurobehavioral function. Lead exposure decreased dopamine binding sites, suggesting excess dopamine availability. The decreased dopamine binding was localized in the nucleus accumbens (mesolimbic dopamine system) but not the dorsal... 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

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