ANS 1: ganglion

sympathetic and parasympathetic, autonomic and somatic, receptors, NA synthesis, NA inhibition

What are the 2 nervous systems

CNS: brain + spinal cord

PNS: Cranial nerves (12 pairs) + spinal nerves (31 pairs)

Draw an overview of the nervous system organisation

What is the function of the peripheral nervous system:

conveys signals between the CNS and the tissues

What neurotransmitter and receptor type are used in the somatic efferent system, and what is the target organ?

Acetylcholine (ACh) binds to nicotinic (nic) receptors on skeletal muscle.

What neurotransmitters and receptors are involved in the sympathetic response for blood vessels and other organs?

Acetylcholine (ACh) binds to nicotinic (nic) receptors at the ganglion, and norepinephrine (NA) is released at the target organs like blood vessels.

What neurotransmitters and receptors are involved in the sympathetic innervation of sweat glands?

Acetylcholine (ACh) binds to nicotinic (nic) receptors at the ganglion, and ACh binds to muscarinic (mus) receptors on the sweat glands.

What neurotransmitter and receptor type are involved in the adrenal medulla's activation in the sympathetic system?

Acetylcholine (ACh) binds to nicotinic (nic) receptors on the adrenal medulla, which then releases epinephrine into the bloodstream.

What neurotransmitters and receptors are involved in the parasympathetic system?

Acetylcholine (ACh) binds to nicotinic (nic) receptors at the ganglion, and ACh binds to muscarinic (mus) receptors on glands, smooth muscles, and the heart.

What is the autonomic nervous system

Automatic

subconscious control of organs and homeostasis

controls all outputs from CNS to the body except to skeletal muscle that is controlled by somatic efferent system

Give a brief overview of sympathetic and parasympathetic systems

• Consists of pre and post-ganglionic

Describe Preganglionic Neuron

Cell body in CNS

Small diameter & myelinated

Synapses at autonomic ganglia

Releases ACh (acetylcholine)

ACh acts on nicotinic receptors on post synaptic neuron

Describe Postganglionic Neuron

• Cell body in autonomic ganglion

• Small diameter & unmyelinated

• Synapses close to target organ

What is the exception with adrenal medulla

Adrenal medulla is the specialised ganglion and chromaffin cells are specialised post synaptic neuron

What is the autonomic ganglion, location, neurotransmitter, function

Location: between pre and post ganglionic neurons of ANS

Neurotransmitter: ACh

Function: Generates a fast Excitatory post synaptic potential via ganglionic nicotinic ACh receptors, conducts Na+ in and K+ out

Which organs are controlled by sympathetic and parasympathetic nervous system

How does the ANS regulate the heart

• controls heart rate

• contracts + relaxes smooth muscle in blood vessels and organs

• glandular secretion

• metabolism

What happens when the ANS stimulates ganglionic nicotinic receptor

• Activates sympathetic and parasympathetic post-synaptic nerve

• Secretes adrenaline from adrenal medulla

• Sympathetic responses dominate

• tachycardia, increase in BP, increase in secretions

Name 2 ganglion blocking drugs, MOA and uses

Hexamethonium: binds to nic receptor, blocks ACh but doesn’t contract muscle, used to relax e.g. anti-hypertensives

Local anaesthetic: blocks pain receptors in SNS + given with adregenic receptors (regulate BP, HR) e.g. lidocaine

What are the key features of the sympathetic nervous system regarding transmitters at the target organ? e.g. what do post synaptic sympathetic fibres release, where is NA stored

Most postsynaptic sympathetic fibers release noradrenaline (NA). Cell bodies are located in sympathetic ganglia and send axons that end in varicosities, where noradrenaline is synthesized, stored, and released.

except sweat glands release ACh and Renal vessels release dopamine

What does the adrenal medulla release

It also releases adrenaline like a post synaptic nerve

Where does NA act and what is its effect

Receptors a1,a2,b1

effect: vasoconstriction, increased heart rate

How is Noradrenaline synthesised

1. L-tyrosine is the precursor

2. Converted by tyrosine hydroxylase into L-DOPA (rate-limiting step)

3. L-DOPA is decarboxylated by DOPA decarboxylase into dopamine

4. Dopamine is converted into noradrenaline by dopamine β-hydroxylase on the membrane of synaptic vesicles

5. In chromaffin cells, noradrenaline is converted to adrenaline by phenylethanolamine N-methyltransferase

How are neurotransmitters synthesised overall

• Synthesis of enzymes in cell body

• Slow axonal transport of enzymes

• Synthesis and packaging of neurotransmitter at nerve terminal

• Release and diffusion of neurotransmitter into synapse

• Postganglionic fibers send axons to target organ

• Enzymes for synthesis made in cell body, transported to the nerve terminus, where the transmitter is made at terminal varicosities

NA SYNTHESIS: How and what does Metirosine inhibit and what are the side effects

Metirosine inhibits tyrosine hydroxylase (1º enzyme) , inhibits NA

Useful for treating catecholamine (stress hormone) tumours

S/E: Headaches, heavy sweating, rapid HR, High BP

NA SYNTHESIS: How and what does Carbidopa

Inhibits DOPA decarboxylase (2º enzyme), prevents dopamine and NA

Used: Parkinson’s disease by blocking L-DOPA

Effects: reduces L-DOPA effects on periphery, reduces HR/BP

ADV: doesn’t cross BBB ↑Availability in CNS

How is noradrenaline release regulated (hint: Action potentials)

• Ca2+ channels open due to depolarisation

• Leads to vesicle exocytosis

• NA released

• activates presynaptic receptors that inhibit adenylyl cyclase

• Prevents Ca2+ opening again, limits further release if NA

Termination of Noradrenergic Transmission - Uptake 1

• Key Term: Neuronal Epinephrine Transporter (NET)

• Location: Presynaptic nerve terminals

• Function: Actively transports noradrenaline (NA) back into nerve varicosities

• Recycling: Recycles ~70% of NA

• Storage: NA taken up into vesicles by Vesicular Monoamine Transporter (VMAT)

• Co-transmitter: ATP stored with NA, prevents leakage, co-released with NA

Termination of Noradrenergic Transmission - Uptake 2

• Key Term: Extraneuronal Monoamine Transporter (EMT)

• Location: Postsynaptic cell

• Function: Actively transports catecholamines into the postsynaptic cell

• Metabolism: Catecholamines metabolized by Catechol o-Methyl Transferase (COMT)

How else can NA transmission be terminated

Metabolism VIA:

Monoamine oxidase

Catechol-methyl transferase

How does methyldopa inhibit the release of NA

False precursor methyl NA

a2 agonist

inhibits DOPA decarboxylase

Effect: relaxes Blood vessels, treats HBP, preferred for pregnancy

How does Guanethidine inhibit the release of NA

Substrate for NET

Substrate for VMAT

Accumulates in vesicles

Stabilises vesicles

Displaces NA (slowly)

Free NA metabolised by MAO

High doses – destroys neuron

Overall effect: block of adrenergic neurons

Historically used as antihypertensive

How does reserpine inhibit the release of NA

-Inhibits VMAT

-Prevents transport of NA into vesicles

-NA metabolised by MAO

used as hypertensive

useful experimental tool

What are some unwanted effects of inhibiting NA synthesis/release

• Hypotension

  Bradycardia

  Digestive disorders

  Nasal congestion

  Sexual dysfunction

  Central effects common (i.e. not directly via autonomic system)

  Sedation

  Mood disturbances

  Less with carbidopa - does not enter CNS