Chemical transmitters, norepinephrine

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

The taste receptor mechanism has been more fully described by Kurihara (1987). The process from chemical stimulation to transmitter release is schematically presented in Figure 7-4. The receptor membranes contain voltage-dependent calcium channels. Taste compounds contact the taste cells and depolarize the receptor membrane this depolarization spreads to the synaptic area, activating the voltage-dependent calcium channels. Influx of calcium triggers the release of the transmitter norepinephrine. 

This interest in the nature of chemical transmission in the central nervous system continues to bear fruit. For example, studies on nerve terminals of postganglionic adrenergic fibers (6) and on the adrenal medulla had, over a period of many years, provided a fairly clear picture of the biosynthesis, release, reuptake, and destruction of the adrenergic transmitter norepinephrine. Other studies had shown that in patients with classical Parkinson s disease parts of the brain—the substantia nigra and corpus striatum—contained less dopamine than did normal brains (7). Dopamine is one of the intermediates in the biosynthesis of norepinephrine from phenylalanine. 

The tricyclic antidepressants inhibit the activity of the uptake mechanism by which some chemical transmitters (serotonin (5-HT) or noradrenaline (norepinephrine)) re-enter nerve endings in the CNS. In this way they raise the concentrations of the chemical transmitter in the receptor area. If depression represents some inadequacy in transmission between the nerves in the brain, increasing the amount of transmitter may go some way towards reversing this by improving transmission. 

N euro transmitters are chemical substances called neurohormones. These are released at Hie nerve ending that facilitate the transmission of nerve impulses. The two neurohormones (neurotransmitters) of the sympathetic nervous system are epinephrine and norepinephrine Epinephrine is secreted by the adrenal medulla Norepinephrine is secreted mainly at nerve ending of sympathetic (also called adrenergic) nerve fibers (Pig. 22-2). 

The chemical structure of histamine has similarities to the structures of other biogenic amines, but important differences also exist. Chemically, histamine is 2-(4-imidazolyl)ethylamine (Fig. 14-1). The ethylamine backbone is a common feature of many of the amine transmitters (e.g. dopamine, norepinephrine and serotonin). However, the imidazole nucleus, absent from other known transmitters, endows histamine with several distinct chemical properties. Among these is prototypic tautomerism, a property that permits it to exist in two different chemical forms (Fig. 14-1). The tautomeric properties of histamine are thought to be critical in the... 

Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6-4. Presynaptic regulation by a variety of endogenous chemicals probably occurs in all nerve fibers. 

Neurons in the central nervous system communicate by chemical transmission. Of relevance to the present discussion are monoamine neurons that release dopamine, norepinephrine, or serotonin as one of their transmitters in response to an action potential. Reuptake transporter proteins embedded in the neuronal plasma membrane then clear the synapse of monoamines, typically taking up 70-80%) of the released transmitter. This reuptake is thought to be the major termination mechanism for the monoamine chemical signaling process. 

My guess is that serotonin will be found to be part of the equilibrated system of chemical controls of smooth muscle and that the gross effects most of us study with present crude methods bear little relationship to the physiological mechanisms of the circulation. The story may well have a parallel with norepinephrine. Until von Euler got the idea that norepinephrine was a transmitter, and then distinguished between exogenous and endogenous stores, the understanding of this catecholamine was pretty muddy as well. 

The story of norepinephrine, which is so inextricably associated with the names of my friends, Ulf v. Euler (2) and Peter Holtz (6), needs no telling again by me. It has grown in our lifetime from very uncertain observations to a great body of fact. Preventing its transmitter function at the myoneural junction in patients has proved one of the key mechanisms by which elevated blood pressure can be lowered. Clearly, the catecholamines occupy a critical position in the chemical regulation of tissue perfusion. 

Many foods and beverages (e.g., wine, cheese, and chocolate) contain tyramine. This chemical is normally degraded by MAOa, before systemic absorption. When the inhibition of MAOa occurs, due to the administration of these drugs, tyramine from ingested food is absorbed. It is then taken up into adrenergic neurons, where it enters the synthetic pathway and is converted to octopamine. a false transmitter. This results in a massive release of norepinephrine, and may result in a hypertensive crisis. 

When a nerve impulse arrives at a synapse, it causes the release of a minute amount of a chemical substance called a neurotransmitter (or synaptic transmitter) which is a localized hormone. This substance diffuses across the gap and, on reaching the far side, it interacts with receptors (on the postsynaptic membrane of a muscle or nerve cell. As soon as it has acted, the neurotransmitter is removed from the synaptic cleft, either by reabsorption into the presynaptic store (norepinephrine) or by enzymic destruction (acetylcholine). In this way, the synapse is rapidly restored to its resting state and is then ready to respond to another impulse. 

The earliest experiments of this type employed voltammetry as a detection scheme. Fast-scan cyclic voltammetry can be used to discriminate between released substances with different oxidation/reduction properties. Voltammetric measurements of absolute concentrations released from single vesicles undergoing exocytosis have proven to be difficult however, because the amount of transmitter released is only at zeptomole levels and because the events occur on the millisecond time scale [13]. Furthermore, although elicited by chemical stimulation, these events do not occur at precise times. Although several neurotransmitters have been identified on the basis of characteristic voltammograms, it is difficult to distinguish catecholamines with this technique. However, fast-scan cyclic voltammetry has been used to identify the seaeted catecholamines norepinephrine and epinephrine [14]. 

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