Adrenergic Pharmacology Quiz

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At a typical sympathetic noradrenergic junction, which process rapidly ends most of the local transmitter signal?

A Breakdown by monoamine oxidase in the synaptic cleft
B Diffusion out of the cleft into the bloodstream, where it is metabolised elsewhere
C Reuptake into the presynaptic terminal through NET ✓
D Hydrolysis in the cleft by acetylcholinesterase
E Extraneuronal metabolism by catechol-O-methyltransferase (COMT) in surrounding tissues

The answer is C: Reuptake into the presynaptic terminal through NET

Explanation

Why C is correct

See The Adrenergic Terminal. Option C is correct because the main rapid way a sympathetic nerve ends its noradrenaline signal is reuptake through the norepinephrine transporter (NET). Noradrenaline, called norepinephrine in the United States, is the transmitter released by most sympathetic postganglionic terminals (the nerve endings that connect to the target organ). NET is a transporter, a protein pump in the terminal's membrane, that pulls noradrenaline back into the nerve ending within moments of release. Once inside, the transmitter has two fates: the vesicular monoamine transporter (VMAT) can reload it into storage vesicles for reuse, or monoamine oxidase (MAO), an enzyme in the mitochondria, can break it down. Catechol-O-methyltransferase (COMT) matters mainly outside the neurone and for circulating catecholamines, so metabolism completes the disposal while reuptake ends the signal. This is different from cholinergic synapses, where an enzyme, acetylcholinesterase, destroys the transmitter in the cleft. Memory aid: acetylcholine is broken down, noradrenaline is brought back.

Main off-switch: reuptake of noradrenaline through the norepinephrine transporter (NET).
After reuptake: VMAT reloads it into vesicles or monoamine oxidase breaks it down.
COMT: acts mainly outside the neurone and on circulating catecholamines.
Contrast: acetylcholine is broken down in the cleft, but noradrenaline is brought back.

Why the other options are incorrect

A. Breakdown by monoamine oxidase in the synaptic cleft: Monoamine oxidase is an enzyme inside the neurone, in the mitochondria, not in the cleft. It disposes of noradrenaline after it has been taken back up, so it follows reuptake rather than ending the signal itself.
B. Diffusion out of the cleft into the bloodstream, where it is metabolised elsewhere: Some transmitter does escape, and circulating catecholamines are metabolised elsewhere in the body. This is a slower, secondary route and is not the main rapid way the local signal is ended.
D. Hydrolysis in the cleft by acetylcholinesterase: Acetylcholinesterase is the enzyme that ends the acetylcholine signal at cholinergic synapses. It does not break down noradrenaline, so it is the off-switch for a different transmitter.
E. Extraneuronal metabolism by catechol-O-methyltransferase (COMT) in surrounding tissues: COMT is important outside the neurone and for circulating catecholamines, but it is not the chief enzyme acting in the cleft. It completes disposal in the wider tissue rather than ending most local signalling.

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