Neurotransmitter-receptor interactions

Once the electrical signal has arrived at a chemical synapse (see Fig 4.2) a cascade of events is triggered with the arrival of an electrical impulse (an action potential), a chemical compound known as a neurotransmitter is released from the presynaptic side into the synaptic cleft. The released neurotransmitter then reaches the membrane of the second cell (postsynaptic membrane) where it interacts with a macromolecule, a so-called receptor. It is this neurotransmitter receptor interaction that triggers another cascade of (chemical) reactions within the second cell and this ultimately leads to the generation of an electrical signal within this cell. This signal then is transferred along this second cell s axon towards another synapse. 

We emphasize that these theories are not mutually exclusive. Thus, a genetically determined membrane defect could produce a dysregulation in the neurotransmitter-receptor interaction. This, in turn, may impact second messenger systems within specific neural circuits, resulting in a disturbance of biological rhythms such as neuroendocrine function. 

D. J. Triggle, Neurotransmitter-Receptor Interactions, p. 80, Academic Press, London (1971). 

Triggle, D.J. "Neurotransmitter-Receptor Interactions," Academic Press, New York, (1971), p. 209. 

Phenothiazine cholinesterase inhibitors. Synthetic derivatives of phe-nothiazine are well-tolerated drugs against a variety of human ailments from psychosis to cancer. A number of synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. Phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of AD [165],... 

Alternatively, the neurotransmitter/receptor interaction leads to the activation or deactivation of enzymes. In Chapter 5, this was represented as a direct process whereby the receptor and target enzyme are closely associated. In reality, the receptor and target enzyme are not directly associated and the interaction of receptor and neurotransmitter is the first step in a complex chain of events which involves several proteins and enzymes. 

Cyclic AMP has been implicated in synaptic transmission due to its actions on a number of important synaptic and neuronal events, such as membrane permeability, synaptic membrane phosphorylation, neurotransmitter synthesis, and cell growth and differentiation. As pointed out earlier, neurotransmitter-receptor interactions can result in direct physical perturbations of the membrane with consequent alterations in membrane permeability to specific ions. This effect is particularly the case when the ionophore is located near the receptor. However, if the ionic channel is distant from the receptor, mechanisms such as phosphorylation can result in an alteration of channel permeability. Cyclic AMP is known to lead to a hyperpolarization of neurons in a number of brain regions such as the cerebral cortex, the caudate nucleus, the peripheral paravertebral sympathetic ganglia, the cerebellar cortex, and the hippocampus. Although it has been hypothesized that this hyperpolarization is the consequence of the phosphorylation of specific neuronal membrane proteins, the relatively short duration of hyperpolarization... 

Neuropeptides are neurotransmitters, which are biomolecules that transmit chemical messages along nerve pathways. They act by connecting with other molecules (or parts of molecules) called receptors. The neurotransmitter-receptor interaction plays an important role in the effects on the body of both poisons and medicines. 

People who have built up a drug tolerance often respond to the attenuated effect by increasing the dose administered. As the dose increases, the neurons readjust again by further down-regulating receptors. Consequendy, addicts may not experience a euphoric, psychoactive sensation, but will continue using the drug to avoid uncomfortable feelings associated with a low level of neurotransmitter-receptor interaction. 

Most hormones and neurotransmitters can interact with more than one receptor subtype. The different receptor isoforms may differ in their ligand-binding properties,... 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

These approaches to receptor identification and classification were, of course, pioneered by studies with peripheral systems and isolated tissues. They are more difficult to apply to the CNS, especially in in vivo experiments, where responses depend on a complex set of interacting systems and the actual drug concentration at the receptors of interest is rarely known. However, the development of in vitro preparations (acute brain slices, organotypic brain slice cultures, tissue-cultured neurons and acutely dissociated neuronal and glial cell preparations) has allowed more quantitative pharmacological techniques to be applied to the action of drugs at neurotransmitter receptors while the development of new recording methods such as patch-clamp... 

Dopamine (69) is a well-known neurotransmitter which interacts with many receptors in the central... 

This seventh edition includes discussions of neurotransmitters ranging from acetylcholine through other amines, amino acids, purines, peptides, steroids and lipids Whereas in most cases their metabolism and receptor interactions are known, much current research involves questions of identification of effector pathways, their regulation and control. 

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