Neurotransmitter receptors functions

Changes in neurotransmitter receptor function and density on platelets and lymphocytes from patients before and following effective treatment. 

In SUMMARY, irrespective of the specificity of the antidepressants following their acute administration, it can be speculated that a common feature of all these drugs is to correct the abnormality in neurotransmitter receptor function. Such an effect of chronic antidepressant treatment may parallel the time of onset of the therapeutic response and contribute to the receptor sensitivity hypothesis of depression and the common mode of action of antidepressants. 

Seeburg PH, Hartner J. Regulation of ion channel/neurotransmitter receptor function by RNA editing. Curr Opin Neurobiol 2003 13(3) 279-283. 

Several psychological disorders are currently being discussed in terms of the effect of the physical state of the membrane lipids on neurotransmitter receptor function. Hibbeln and Salem (1995) suggest that serotonin levels and membrane 22 6n-3 content are directly linked, whereby low 22 6n-3 yields low serotonin. This results in an individual being susceptible to depression or other affective diseases. These authors suggest that the depletion of 22 6n-3 induces a change in membrane physical properties, which, in turn, influences the function of either serotonergic receptors or serotonin reuptake systems. 

The importance of investigating how cholesterol content and acyl chain composition alter the physical properties of membranes is highlighted by the functional deficits associated with 22 6n-3-deficient diets and the antisocial behavior associated with varied cholesterol levels. In the context of psychological disease and neurotransmitter receptor function, it is important to investigate how compositionally induced changes in membrane physical properties influence membrane-associated signaling processes. 

There are currently two dominant theories as to the etiology of schizophrenia. The most popular postulates abnormal neurotransmitter receptor function within the brain and, to a large extent, concentrates on studying dopamine and serotonin. Although this theory still provides psychiatry with its best tools for dealing with psychosis, namely medications, it has proved sterile ground for developing radical new treatment approaches. 

Seth PK, Hong JS, Kilts CD, et al. 1981. Alteration of cerebral neurotransmitter receptor function by exposure of rats to manganese. Toxicol Lett 9 247-254. 

GABAb receptors mediate the slow and prolonged physiological effects of the inhibitory neurotransmitter GABA. Functional GABAb receptors are comprised of two subunits, GABAbR1 and GABAbR2. Both subunits are G-protein-coupled receptors, which couple to the Gi/o family and are densely expressed at spinal nociceptive synapses. 

The aim of this chapter is to consider the structure, distribution and functional properties of neurotransmitter receptors in the brain in general and discuss the principles of how the action of drugs at these receptors can be studied. (See relevant Chapters for detail of individual NT receptors.)... 

Neurotransmitter receptors have evolved as one of the key components in the ability of the central nervous system to coordinate the behaviour of the whole animal, to process and respond to sensory input, and to adapt to change in the environment. These same receptors are therefore ideal targets for drug action because of their central role in the activity of the nervous system. A rational approach to the development of new therapeutic strategies involving the action of drugs at receptors in the nervous system is based on knowledge of receptor structure, distribution and function. 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

O Classic views as to the cause of major depressive disorder focus on the monoamine neurotransmitters norepinephrine (NE), serotonin (5-HT), and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning. 

The neurotransmitter receptor hypothesis suggests that depression is related to abnormal functioning of neurotransmitter receptors. In this model, antidepressants presumably exert therapeutic effects by altering receptor sensitivity. In fact,... 

Regulation of neurotransmitter receptors the p-adren-ergic receptor. This receptor, of which three subtypes have been cloned, mediates many of the effects of norepinephrine and epinephrine in the brain and peripheral tissues. One of the dramatic features of P-adrenergic receptor function is its rapid desensitization in response to agonist stimulation. It is now known that one important mechanism for this desensitization is phosphorylation of the receptor both by PKA and by a receptor-associated protein kinase, PARK (also called GRK2 Fig. 23-6). 

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