Adrenergic transmitters

Invertebrates contain the trace amines OCT and TYR, which are the invertebrate counterparts of the vertebrate adrenergic transmitters NE and adrenaline. Invertebrate OCT and TYR occur at much higher... 

Because of its motor, i.e., activating effect on vascular smooth muscle and its inhibitory effect on intestinal smooth muscle, the sympathetic nervous system has been cast into the role of the component of the nervous system that executes control of visceral function in times of physical emergency for the organism. The phrase fight or flight has been often used to describe the circumstances in which the adrenergic transmitters of the sympathetic system are dominant over the cholinergic parasympathetic system. This concept is perhaps oversimplified but it has the utility of a first approximation of how the two components of the ANS interact in the periphery. Sensory inputs which lead to increased blood pressure, for example, activate the sympathetic pathways. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

Central nervous system effects adrenergic transmitter agent at synapses no brain excitation... 

Glisson, S.N., Karezmar, A.G. and Barnes, L., 1972. Cholinergic effects on adrenergic transmitters In rabbit brain parts. Neuropharmacol. 11 456-477. 

M. Israel and M. Tomasi, A chemiluminescent catecholamine assay its application for monitoring adrenergic transmitter release, J. Neurosci. Methods., 91, 101-107 (1999). 

We have already noted that a fentanyl derivative was used in Russia in 2002 to end the Moscow theatre hostage crisis. In the United States such agents and related opioids were still being researched in the early 1990s, as were agents that could affect a2-adrenergic transmitter/ receptor systems.37 Also, some of the natural agents understood... 

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. 

Physiology is the study of function. The classical procedure used to define physiological roles is by extirpation, ablation or nerve section to reveal inadequate or inappropriate function in the absence of the postulated mechanism. This approach cannot be used to study the physiological role of arachidonate metabolites since they are not organ-localized like the adrenal steroids or concentrated in specific cells like the adrenergic transmitters. The problem is compounded also by the fact that arachidonate oxygenation is almost a universal phenomenon. Finally the metabolites are not stored like histamine or serotonin but are released immediately upon synthesis. Consequently it is always necessary to initiate synthesis to study release. Thus release is synonymous with synthesis. 

S.2.9.2. Formation, Storage and Release of False Adrenergic Transmitters 52.9.2.1. Biosynthesis of False Transmitters... 

More recently a number of related amino acids have been tested as possible precursors for the formation of false adrenergic transmitters. Among these compounds the amino acids 5-hydroxyDOPA and its methoxylated derivative 4-methoxy, 3,5-dihydroxyphenylalanine (Fig. 11) have proved of interest. These compounds give rise to the corresponding decarboxylated and ) -hydroxylated amines which are stored in the adrenergic nerves. There is, however, some tissue selectivity with a much larger proportion of the NA in peripheral sympathetic nerves being replaced by the false amines than in the CNS, presumably because the parent amino acids enter the brain only slowly. 

Although the concept of false transmitters as substances with weaker agonist activity diluting the normal stores of adrenergic transmitter is attractively simple and elegant, the true pharmacological situation is in fact quite complex. The overall effect of the introduction of a false transmitter on adrenergic neurotransmission depends on a number of different factors. 

The false adrenergic transmitters, a-methylnoreiniiephrine and metaraminol (see Sect. B, Chap. 5.2), displace the naturally occurring NAt from its binding sites in many tissues, including adipose tissue. 

Compounds affecting adrenergic transmitters - Fusaric acid amide (XIV, Sch 10595) is a very active inhibitor of dopamine-3"hydroxy1ase in vivo (but not in vitro), and it lowers the blood pressure of DOCA hypertensive rats for many hours in a dose-related manner.53 The cyclohexylamino-oxazoline (XV, BAY a678i) probably exerts its hypotensive effect by preventing the release of catecholamines from the adrenal gland.5 3-Ethyl-a-methyltyrosine (XVl) is a competitive inhibitor of tyrosine hydroxylase and exhibits significant anti hypertensive activity in DOCA rats at 25 mg/kg. It may be preferable to a-methyltyrosine because it should not be metabolised into a catechol amine.55... 

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