Norepinephrine recapture

Removal of norepinephrine Norepinephrine may (1) diffuse out of the synaptic space and enter the general circulation, (2) be metabolized to O-methylated derivatives by post-synaptic cell membrane-associated catechol O-methyltransferase (COMT) in the synaptic space, or (3) be recaptured by an uptake system that pulls the norepinephrine back into the neuron. The uptake by the neuronal membrane involves a sodium-potassium activated ATPase that can be inhibited by tricyclic antidepressants such as imipramine (see p. 119), or by cocaine (see Figure 6.3). 

Potential fates of recaptured norepinephrine Once norepinephrine reenters the cytoplasm of the adrenergic neuron it may be taken up into adrenergic vesicles via the amine transporter system and be sequestered for release by another action potential or persist in a protected pool. Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria. The inactive products of norepinephrine metabolism are excreted in the urine as vanillylmandelic acid (VMA), metanephrine and normetanephrine. 

In addition to terminating the actions of released monoamines, the plasma membrane monoamine transporters present at neuronal locations function in sequence with vesicular monoamme transporters to recycle catecholamines for rerelease (Figure 29-3). Thus most of the norepinephrine released and recaptured by sympathetic nerves is sequestered back into storage vesicles, thereby substantially reducing the requirements for synthesis of new transmitter. 

Keuptake of norepinephrine by a higli-affiniiy iranspon system (Uptake ) in the nerve terminals recaptures most of the transmitter and is the main nit thod of temiinaung its effects. A similar (extraneu-rona ) transport system (Uptake 2) exists in the tissues but is less selective and less easily satiitaied. 

MAO, which is the enzyme that inactivates norepinephrine and serotonin. The third type of drug action is represented by Prozac, which prevents the recapture of serotonin by neurons that release it. Drugs of this type, (Zoloft is another), known as selective serotonin re-uptake inhibitors (SSRIs), have become the drugs of choice for treating serious clinical depression. For each of these three classes of drugs, the msgor mechanism of action is to increase the concentration of neurotransmitters at synapses. 

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