Noradrenergic Neurotransmission

What are Catecholamines

Give 3 examples

Catecholamines are signalling molecules derived from tyrosine. They include noradrenaline, dopamine and adrenaline

What is the process of noradrenergic neurotransmission

1. Noradrenergic neuron takes up tyrosine via carrier-mediated transport

2. Tyrosine —(tyrosine decarboxylase)→ DOPA —(DOPA decarboxylase)→ Dopamine

3. Dopamine stored in vesicles by a specific transporter protein (VMAT - Vesicular monoamine transporter).

4. In the synaptic vesicles Dopamine —(dopamine-β-hydroxylase)→ Noradrenaline

5. Depolarization by action potential → Ca2+ influx

6. Noradrenaline is released by Ca2+ mediated exocytosis (synaptobrevins & syntaxins form a complex)

7. Noradrenaline binds to alpha or beta adrenoceptors on the post synaptic cleft

8. Noradrenaline action is terminated. It is reuptaken by NAT.  (It is also taken into non-neuronal cells via a lower affinity transporter than NAT)

9.  Noradrenaline is metabolised by monoamine oxidase (MAO), catechol-O-methyl transferase (COMT) & aldehyde dehydrogenase (ADH).

What is the full route of Tyrosine producing all of its derived molecules

Tyrosine —(tyrosine decarboxylase)→ DOPA —(DOPA decarboxylase)→ Dopamine —(dopamine-β-hydroxylase)→ Noradrenaline —(phenylethanolamine N-methyltransferase) → Adrenaline

What decides whether Tyrosine forms dopamine, noradrenaline or adrenaline

Dopaminergic neurons do not have dopamine-β-hydroxylase so do not proceed to noradrenaline.

Noradrenergic neurons do not have phenylethanolamine N- methyltransferase so do not proceed to adrenaline.

The adrenaline-producing cell in the adrenal medulla have all of the enzymes so can make the hormone adrenaline.

We know that there are alpha and beta adrenal receptors, but how many subtypes of each are there

There are two subtypes of alpha and three subtypes of beta receptors:

α1

α2

β1

β2

β3

Main ways to increase neurotransmission

Use agonists to mimic NT

Inhibit enzymes that metabolise NT

(Inhibit transporters responsible for taking NT out of synapse)

Main ways to reduce neurotransmission

Use antagonists to block NT

Inhibit enzymes that synthesise NT