Norepinephrine feedback control

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

The first step is catalysed by the tetrahydrobiopterin-dependent enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), which is regulated by end-product feedback is the rate controlling step in this pathway. A second hydroxylation reaction, that of dopamine to noradrenaline (norepinephrine) (dopamine [3 oxygenase) requires ascorbate (vitamin C). The final reaction is the conversion of noradrenaline (norepinephrine) to adrenaline (epinephrine). This is a methylation step catalysed by phenylethanolamine-jV-methyl transferase (PNMT) in which S-adenosylmethionine (SAM) acts as the methyl group donor. Contrast this with catechol-O-methyl transferase (COMT) which takes part in catecholamine degradation (Section 4.6). 

Biosynthesis of norepinephrine takes piace within adrenergic neurons near the terminus of the axon and junction with the effector cell. The biosynthetic pathway (Fig. 13,1) begins with the active transport of the amino acid L-tyrosine into the adrenergic neuron cell (1). In the first step within the cytoplasm, the enzyme tyrosine hydroxylase (tyrosine-3-monooxygenase) oxidizes the 3 position of tyrosine to form the catechol amino acid L-dopa. This is the rate-limiting step in norepinephrine biosynthesis, and the activity of tyrosine hydroxylase is carefully controlled (3). The enzyme is under feedback inhibition control by product catecholamines and is... 

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