Vesicles, adrenergic synaptic

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

Dopamine -hydroxylase (EC 1.14.17.1) is a glycoprotein which hydroxylates dopamine to norepinephrine during the biosynthesis of catecholamines. The enzyme occurs in the synaptic vesicles of noradrenergic and adrenergic brain... 

This drug depletes neuronal stores of norepinephrine. The drug enters the adrenergic nerve terminus through the synaptic reuptake mechanism, and is transported into the adrenergic vesicle. Once in the vesicle, it displaces norepinephrine from the vesicle to the cytoplasm, where it is degraded by monoamine oxidase (MAO). 

This is a selective a2-adrenergic agonist that suppresses the release of norepinephrine from presynaptic vesicles into the synaptic cleft, thus reducing its concentration, with a consequent improvement in akathisia. 

Considering the chemical structure of ephedrine, it is interesting to observe the lack of the phenolic group, characteristic of catecholamines. However, ephedrine remains capable to stimulate a- and p-receptor directly and displace norepinephrine (NE) from storage vesicles, releasing these catecholamines at synaptic areas in the brain and in the heart. These released substances act on receptors promoting the adrenergic effect [17, 66]. 

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