5-Hydroxytryptamine storage

Reserpine also interferes with the neuronal storage of a variety of central transmitter amines such that significant depletion of norepinephrine, dopamine, and 5-hydroxytryptamine (serotonin) occurs. This central transmitter depletion is responsible for the sedation and other CNS side effects associated with reserpine therapy. The depletion of brain amines also may contribute to the antihypertensive effects of reserpine. 

Reserpine is a Rauwolfia alkaloid that has been used for centuries to treat insanity, insomnia and hypertension in humans. Reserpine inhibits normal sympathetic activity in both the CNS and the peripheral nervous system by binding to catecholamine storage vesicles, causing catecholamines to leak into the synapse so that they are not available for release when the presynaptic neuron is stimulated. This prevents the normal magnesium and ATP-dependent storage of catecholamines and 5-hydroxytryptamine in nerve cells, the result being catecholamine (norepinephrine (noradrenaline)) depletion. This results in the inhibition of normal sympathetic activity. 

As summarized in the review by Clifford (1985b), the terms crude and total lipid refer to substances extracted by a non-polar solvent and may include non-lipid substances such as caffeine. The yield is a function of the extraction method as much as of the composition of the beans. The crude lipid includes the wax coating the coffee bean (0,2-0.3 %), the main constituents of which are the C2o and C22 amides of 5-hydroxytryptamine [l//-indol-5-ol, 3-(2-aminoethyl-), serotonine]. These amides have their importance. As they are possible antioxidants, it has been suggested that premature dewaxing leads to a fall in the bean quality during storage. The major part of the crude lipid is a typical seed oil, with triglycerides of fatty acids, some other esters and unsaponifiable matter. 

A large proportion of the experimental work has involved the analysis of the effects of drugs which are thought to interfere with the synthesis, storage, release or breakdown of 5-hydroxytryptamine. This type of evidence is discussed later (p. 296). Physiological studies, summarized here, have yielded few results to justify the enthusiasm provoked by some of the pharmacological investigations. 

SYNTHESIS, STORAGE, AND RELEASE OF CATECHOLAMINES Synthesis—The steps in the synthesis of DA, NE (known outside the U.S. as noradrenaline), and Epi (known as adrenahne) are shown in Eigure 6-A. Tyrosine is sequentially 3-hydroxylated and decarboxylated to form DA. DA is 3-hydroxylated to yield NE (the transmitter in postganglionic nerves of the sympathetic branch of the ANS), which is N-methylated in chromaffin tissue to give Epi. The enzymes involved are not completely specific consequently, other endogenous substances and some drugs are also substrates. 5-hydroxytryptamine (5-HT, serotonin) can be produced from 5-hydroxy-L-tryptophan by aromatic L-amino acid decarboxylase (AAD or dopa decarboxylase). AAD also converts dopa into DA, and methyldopa to a-methyl-DA, which is converted to a-methyl-NE by dopamine /3-hydroxylase (Dj3H Table 6-4). 

Although vesicles bind either NA or ADR. the storage mechanism is not specific for these amines. Other related compounds can also be bound within medullary or neuronal vesicles. For example, L-metaraminol and p-tyramine can stoichiometrically replace the endogenous catecholamine, without affecting the ATP content of the storage vesicles. Many other amines will bind in a similar manner, e.g. guanethidine and 5-hydroxytryptamine. 

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