ANS Background Flashcards
Divisions of the ANS
Sympathetic (Fight or Flight)
Parasympathetic (Rest & Digest)
Enteric (GIT)
Layout of SNS
Origin: Thoracolumbar (T1 - L2) Short Pre-ganglionic neuron -> Paravetrebral Ganglion Long Post-ganglionic neuron -> Target organ
Layout of PNS
Origin: CN II, VII, IX, X & S 2, 3, 4 Long Pre-ganglionic neuron -> Synaps near Target organ Short Post-Ganglionic Neuron -> Target organ
Neurotransmitters of the ANS
Acetylcholine (ACh)
Noradrenalin (NA)
Non-adrenergic Non-cholinergic (NANC): Serotonin, Dopamine, GABA, Histamine, NO
Where is Acetylcholine (ACh) found?
Pre-ganglionic
Post-ganglionic PNS
(Exception -> also post-ganglionic in sweat glands in SNS)
Where is Noradrenalin (NA) found?
Post-ganglionic SNS
What are the 6 basic steps of Transmission in the ANS?
Possible sites of Drug action?
- Synthesis of neurotransmitter (NT)
- Storage of NT
- Release of NT
- NT-Receptror interaction on Effector cell
- Removal / Degradation / Recycling of NT
- Repair of Effector cell membrane
Describe the synthesis of Ach
- Choline taken up by neuron (in conjunction with Na, via Na/K pump active transport)
- Glucose enters neuron via facilitated transport -> enters mitochondria -> converted to Acetyl-CoA
- Choline + Acetyl CoA = Acetylcholine (ACh) in cytoplasm of neuron
Describe storage and release of Ach at Cholinergic Junction
- ACh stored in vesicles (H released)
- Exocytosis into pre-synaptic cleft
- Binds receptors (reversible)
Describe the degradation of ACh
RAPID
1. Acetylcholine esterase (AChE)
ACh ——————————————-> Choline + Acetate
2. Bound ACh dissociates from receptor and is also broken down (hydrolysed)
3. No ACh enters circulation
4. Plasma-esterases also deactivates ACh immediately
Describe the synthesis and storage of the adrenergic neurotransmitters
- Tyrosine enters neuron with Na via active transport
- RATE LIMITING STEP:
Tyrosine —Tyrosine Hydrolylase—> Dopa - Dopa —-> Dopamine
- Dopamine taken up by vesicle via Vesicle Mono-Amine Transporter (VMAT)
- Dopamine —–B-hydroxylase—-> NA
- NA converted to Adrenalin ONLY IN adrenal medulla by Phenylethanolamine N-methyl-transferase (PNMT)
Describe the release of adrenergic neurotransmitters at Adrenergic Junction
Stored NA leaks out of vesicles. Taken up via active Granular uptake (also dopamine)
B hydroxylase enzyme released with NA during exocytosis
Describe the deactivation and degradation of NA
SLOWER & more COMPLEX than ACh
- Reuptake by adrenergic neuron NA transporter (NAT) - Na facilitated (reuptake 1)
- Removal by circulation -> degradation in the liver
- Active transport and enzymatic degradation in effector cells (reuptake 2)
Describe the negative feedback of the adrenergic neurotransmitters
- High levels of cytosolic NA inhibits tyrosine hydroxylase
2. NA binds to Autoceptors on pre-synaptic neuron (alpha2 receptors
Name the 2 enzymes which metabolise catecholamines
COMT (Catechol-Oxygen-MethylTransferase)
MAO (Mono-Amino-Oxidase)
Name the function and effect of COMT
Methylates the meta hydroxyl group of catecholamines.
Very specific
Lowers activity of NA & adrenaline by 100x
Works rapidly
Name the function and effect of MOA
Deaminates dopamine, tyramine, 5-HTP, amine containing drugs, as well as NA & adrenaline
i.e. Protective - Destroys exogenous biologically active amines.
Not as specific as COMT
Describe the effects of NA binding to alpha 1 receptors
Post-synaptic
Increased production of DAG and IP3 -> increased cellular calcium ions and depolarisation
Describe the effects of NA binding to alpha 2 receptors
Auto-receptors on neuron (pre-synaptic)
Decrease cAMP production -> inhibits further release of NA from neuron
Name the cholinergic receptors and state where these receptors are most likely found
1. Nicotinic: Nn - autonomic ganglia Nm - skeletal muscle (not in ANS) 2. Muscarinic: PNS post-ganglionic M1 - gastric parietal M2 - heart M3 - glands / smooth muscle
Name the adrenergic receptors and state where these receptors are most likely found
alpha 1 -> post-synaptic neurons (esp smooth muscle)
alpha 2 -> pre-synaptic mainly (auto receptors)
beta 1 -> heart, intestinal smooth muscle
beta 2 -> bronchial, uterine, vascular smooth muscle
What overall effect does stimulation of alpha receptors bring about?
Excitation (except in intestinal smooth muscle)
What overall effect does stimulation of the beta receptors bring about?
Inhibition (except in heart)
Where are alpha 1 receptors mostly found?
post-synaptic neurons (esp smooth muscle)
