Dopamine And ACh Flashcards
Which three main nuclei in the brain contains the acetylcholine cell bodies?
- Nucleus basalis
- Septal hippocamptal pathway
- Substantia nigra
How is acetylcholine made?
From choline in the diet and Aceyl-CoA from the Krebs cycle
Combined by acetyltransferase
How is acetylcholine stored?
Packaged into vesicles via vesicular ACh transporter which exchanges 2 x H+ for one molecule of ACh
How is acetylcholine released from it’s vesicle into the synaptic cleft?
Ca influx which is required for movement of the vesicle and docking to the pre-synaptic terminal
What are the three different types of ACh vesicles?
- Readily releasable
- Recycling phase
- Reserve
Which 5 ligand gated nicotinic ion channels does ACh act on?
Muscle nAChRs mature (alpha1)2 + beta1 + delta + e
Embryonic muscle (alpha1)2 + beta1 + delta + gamma
Neuronal nAChRs ganglion (alpha3)2 + (beta4)3
Neuronal nAChRs CNS (alpha4)2 + (beta2)3
Neuronal nAChRs CNS (alpha7)5
Which G-protein coupled muscarinic receptors do ACh work on?
M1 - Gq and GII M2 - Go and Gi M3 - Gq and GII M4 - Go and Gi M5 - Gq and GII
What are the two nicotinic ACh receptors?
Four transmembrane domain and ACh binding site
Heteropentomer - 2 x alpha 4, 3 x beta2
Homopentomer - 5 x alpha 7
What is the structure of the muscarinic ACh receptor?
7 transmembrane domains
Binding site for ACh found deep in the transmembrane protein
Hydrophilic binding pocket
How does ACh degradation for reuptake occur?
Has to be broken down to Choline and Acetic acid by acetylcholinesterases
Which drugs work on the nicotinic ACh receptors?
Full agonists - suxamethonium, nicotine
Partial agonists - Varenacline
Reversible antagonists - pancronium, vercuronium
Irreversible antagonists - alpha-bungarotoxin
Which drugs work on the muscarinic ACh receptors?
Full agonists - ACh, muscarine, oxotremorine M
Partial agonists - McN-A-343
Reversible antagonists - atropine, ipratropium, benztropine, procyclidine (CNS active)
Which drugs works on the reuptake mechanism of ACh?
Hemicholinium
Which drug works on the degradation pathway of ACh?
Rivastigmine, neostigmine, galatamine
Which recreational drugs work on the Acetylcholine pathway?
Nicotine
Scopolamine
Henbane
Which diseases can be treated with manipulation of the acetylcholine pathway?
Dementia Myasthenia gravis Parkinson’s Motion sickness Analgesia
Which four localised nuclei is Dopamine found in?
- Substantia nigra
- Tubero-hypophyseal pathway
- Mesolimbic pathway
- Mesocortical pathway
How is dopamine synthesised?
Tyrosine from the diet is converted to DOPA by tyrosine hydroxylase. DOPA is converted to dopamine by dopa carboxylase
How is dopamine stored?
In vesicles via vesicular monoamine transporter (VMAT1 + 2)
In exchange for 2 x H+
How is dopamine released from the vesicle?
Ca dependent
What does en passant varicosities mean?
Release of dopamine isn’t just at the end terminus but also through varicosities down the axon
Which receptors does dopamine act on?
D1-like: D1, D5 coupled to Gs
D2-like: D2, 3, 4 coupled to Gi
What is the structure of the dopamine receptors?
7 transmembrane units
Dopamine binding site deep within the hydrophilic pocket inside the membrane protein
Third intracellular loop region dictates which G protein it is coupled to
How does reuptake of dopamine occur?
Via DAT - dopamine active transporter
Goes back into the cell for reuse
What is the end product of dopamine degradation?
Homovanillic acid via either COMT or MAO
Which drugs works on the synthesis of dopamine?
Levo-DOPA
Which drugs work on the storage of dopamine?
Reserpine and methamphetamine
Which drugs work on the release of dopamine?
Amantadine
Which drugs are full agonists at the dopamine receptors?
Dopamine
Apomorphine
Bromocriptine
Which drugs are antagonists at the dopamine receptor?
Haloperidol
Chlorpromazine
Which drugs work at the reuptake system of dopamine?
Cocaine
Bupropion
Methylphenidate
Which drugs work at the degradation stage of dopamine?
MAO inhibitors
COMT inhibitors - entacapone, tolcapone
Which two recreational drugs work on the dopamine pathway?
Cocaine
Amphetamines
Which diseases can be treated via manipulation of the dopamine pathway?
Drug dependence Parkinson’s disease Schizophrenia Nausea/vomiting Hormonal imbalances
