Catecholamines storage

Oxypertine, with its novel stmcture and apparently promising therapeutic characteristics is a drug worthy of further study. Its specificity for catecholamine storage granules has already been exploited as a research tool [167, 170-3, 180 181] and its continued use for this purpose can be expected to yield further fundamental information. 

Drugs Interfering with Catecholamine Storage and Reuptake... 

The fresh leaves of the khat shrub (Catha edulis) are chewed by several millions of people in East Africa and the Arabian peninsula for their euphoric and stimulating properties (284). The rather newly discovered alkaloid cathinone [(S)-a-aminopropiophenone] is responsible for the stimulating properties of khat (284). It has been shown that cathinone induces release at physiological catecholamine storage sites in a manner similar to that of amphetamine. Further results suggest that cathinone and amphetamine produce their stimulant effects via the same dopaminergic mechanism (599). The more recently discovered khat constituents merucathinone, merucathine, and pseudomerucathine were found to have only weak dopamine-releasing effects and were therefore considered unlikely to play an important role in the stimulatory actions of khat leaves (414). 

Geffen LB, Livett BG, Rush RA (1969) Immunohistochemical localization of protein components of catecholamine storage vesicles. J Physiol (London) 204 593-605. 

Reserpine is an alkaloid from plants of the genus Rauwolfia, used in medicine since ancient times in southern Asia, particularly for insanity more recently, reserpine was extensively used in psychiatry but is now obsolete. Reserpine depletes adrenergic nerves of noradrenaline primarily by blocking amine storage within vesicles present in the nerve ending, so reducing stores of releasable transmitter. Its antihypertensive action is due chiefly to peripheral action, but it enters the CNS and depletes catecholamine stores there too this explains the sedation, depression and parkinsonian (extrapyramidal) side effects that can accompany its use. The effects on catecholamine storage persist for days to weeks after it is withdrawn. 

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. 

A characteristic feature of adrenal medullary chromaffin cells is the presence of numerous catecholamine storage granules ranging in size from 100 to 300 nm in diameter. These granules turn brown when exposed to potassium bichromate solutions, ammoniacal silver nitrate, or osmium tetroxide because of the oxidation and polymerization of epinephrine and norepinephrine. This process is known as the chromaffin reaction, hence the terms chromaffin cells and chromaffin granules. At least two kinds of adrenal medullary chromaffin cells have been identified in most animal species based on differences in chromaffin granules. Norepinephrine-producing chromaffin cells possess dense-... 

O Connor DT, Frigon RP. Chromogranin A, the major catecholamine storage vesicle protein. J Biol Chem. 1984 259 3237-3247. 

An important aspect of the preparation and isolation of subcellular particles from brain regions is the criteria by which purity is assessed. Electron microscopy of the various subcellular fractions can provide among the best pieces of evidence for the presence in the preparation of the organelles or subcellular fragments of interest. However, a number of biochemical markers (usually enzymes) that have been established to be present in certain fractions can also be assayed to demonstrate the enrichment of the organelle of interest. For instance, acetylcholinesterase is a common marker for synap-tosomes dopamine-P-hydroxylase is a marker for catecholamine storage vesicles within the synaptosome and cytochrome c oxidase is a marker for mitochondria. Most of the enzymatic markers can be assayed routinely. 

Axelrod, J., 1970, Amphetamine Metabolism, physiological disposition and its effects on catecholamine storage, in International Symposium on Amphetamines and Related Compounds (Proc. Mario Negri Institute for Pharmacological Research, Milan, Italy), Raven Press, New York. 

S.2.4.3. Actions of Reserpine on Catecholamine Storage (see also Sect. B, Para. S.3.7)... 

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