ST 4.2: Amine Transmitters

Types of amine transmitters

Catecholamines, Serotonin, Histamine

Examples of catecholamines

Dopamine, NE, Epinephrine

Structure of amine transmitters

Catechol group + amino group

Neural origins of amine transmitters

Clusters in the brainstem and the peripheral sympathetic ganglion neurons

Role of amine transmitters?

Modulation of synaptic activity

Catecholamine biosynthetic pathway Step 1

Tyrosine --> L-DOPA

Catecholamine biosynthetic pathway Step 1 Enzyme

Tyrosine Hydroxylase

Catecholamine biosynthetic pathway Step 1 Cofactors

O2, Fe2, BH4

What is the rate-limiting step in the biosynthetic pathway

STEP 1: Tyrosine --> L-DOPA

Catecholamine biosynthetic pathway Step 2

L-DOPA --> Dopamine

Catecholamine biosynthetic pathway Step 2 Enzyme

AAAD

AAAD acts on...

all aromatic L-amino acids.

Catecholamine biosynthetic pathway Step 3

Dopamine --> Norepinephrine

Catecholamine biosynthetic pathway Step 3 Enzyme

Dopamine-Beta-Hydroxylase

Catecholamine biosynthetic pathway Step 4

Norepinephrine --> Epinephrine

Catecholamine biosynthetic pathway Step 4 Enzyme

PNMT

The catecholamine released is determined by what?

The enzyme expressed

Explain negative feedback in the catecholamine biosynthetic pathway.

High levels of DA, NE, or EPI provide feedback to inhibit Tyrosine Hydroxylase

Explain activity dependent regulation of the catecholamine biosynthetic pathway.

An AP triggers Ca2+ influx, Ca2+ activates CAMK2, CAMK2 phosphorylates Tyrosine Hydroxylase. Phosphorylated tyrosine hydroxylase has an increased affinity for BH4 --> increased catecholamine synthesis.

How are all amines transported into synaptic vesicles?

VMAT (Vesicular Monoamine Transporters)

How is VMAT blocked?

Reserpine

How do neurons reuptake amine transmitters from the synapse?

Specific reuptake transporters.

Sagawa Syndrome is caused by

a gene mutation for a gene that encodes the rate-limiting enzyme for BH4. BH4 is critical for producing DA, Serotonin, and Norepinephrine.

What is the focus of Parkinson's treament?

Restoring DA levels in the striatum.

Cause of Parkinson's

Loss of neurons in the substantia nigra reducing dopamine production.

Parkinson's Treatment

L-DOPA (with AAAD inhibitor) or DA receptor antagonist.

What is MPTP Toxicity?

MPTP is converted to MPP+ by MAO. MPP+ is taken up by dopamine transporters and poisons the ETC, killing dopamine terminals.

What do cocaine and amphetamines interfere with?

Dopamine reuptake transporters.