WK4-Adrenergic Synapse

what are the 2 branches of the autonomic system

1. rest & digest system (PSNS)

2. Fight or flight system (SNS)

what is the synapse

where 2 neurons communicate in one direction

• it is the cleft between the preganglionic & post ganglionic

what is the main neurotransmitter for sympathetic nervous system

Noradrenaline , which is also known as norepinephrine

• it is fight or flight which increase heart rate

how is noradrenaline regulated

1. synthesis of norepinephrine takes place

2. dopamine enters the vesicle which is converted to norepinephrine

3. neurotransmitter is released so a influx of calcium causes fusion of the vesicle with the cell known as exocytosis - release is then blocked by guanethidine

4. the postsynaptic receptor is then activated by the binding of the neurotransmitter

5. norepinephrine is then released & rapidly taken into the neuron

6. NA is finally metabolised & broken down by COMT & oxidised by MA O

how is noradrenaline synthesised

1. phenylalanine hydroxylase converts phenylalanine to tyrosine by adding on a -OH group

2. Tyrosine Hydroxylase then convert tyrosine to L-dopa by adding another -OH group

3. DOPA Decarboxylase then covert L-DOPA to dopamine by removing -COOH (activating the dopamine)

4. Dopamine B-hydroxylase is then used to convert dopamine to Noradrenaline by adding -OH to the side chain

what happens when a vesicle contain VMAT (vesicular monoamine transporter)

it is powered by a proton gradient , so when monoamine OR NA is pumped in, a proton is pumped out

what triggers the release of NA

action potential , as it travels across the presynaptic neurons to depolarise & repolarise

what is noradrenaline metabolism

it allows termination of a signal

• NA is metabolised by the 2 intracellular enzymes MONOAMINE OXIDE (MAO) & Catechol-o-methyl transferase (COMT)

what is GDP & GTP bound

GDP is inactive whereas GTP is active

what are the 5 subtypes for adrenergic receptors

Alpha 1

alpha 2

beta 1

beta 2

beta 3

they used G proteins & activate second messengers

describe the location, type of GPCR & basic pathway of Alpha 1

• it is located in the sooth muscle

• it is a Gq gpcr which activates

• it increase in PLC, IP3, intracellular calcium

describe the location, type of GPCR & basic pathway of Alpha 2

• it is found in the presynaptic nerves

• it is a Gi(inhibition) GPCR

• it decreases the activation of Adenylate cyclase

• decrease in cAMP

describe the location, type of GPCR & basic pathway Beta 1,2,3

it is found in the heart, smooth muscle & fatty tissue

• it is a Gs(stimulation) GPCR

• it increases activation of Adenylate cyclase

• increase cAMP

• increases intracellular signalling pathway

describe alpha 1 adrenergic receptor signalling

it is found in smooth muscle cell which causes contraction

• it uses the Gq protein, so NA brings the leads of activating PLC

• it then catalyses PIP2 to break down to DAG and IP3. This cause IP3 to open up calcium channels on the endoplasmic reticulum which increases the cytoplasmic calcium conc.

describe alpha 2 adrenergic receptor signalling

Alpha 2 receptors inhibit the release of from the presynaptic nerve

1. binding of NA causes the release of the inhibitory Gi protein

2. this become active & inactivates the adenylate cyclase by inhibiting it

3. this causes a decrease in cAMP & inactivate PKA & voltage gated calcium channels

describe beta 1 adrenergic receptor signalling

it is found in cardiac muscle which stimulates contraction

1. NA binding activates adenylate cyclase

2. this increases cAMP levels & activates PKA

3. it then opens plasma membranes & SR calcium channel which increase cytoplasmic calcium concentration

describe beta 2 adrenergic receptor signalling

it is found in the lung of smooth muscle cells which stimulates bronchodilation

1. NA then binds & stimulates adenylates cyclase

2. this increase cAMP levels which PKA

3. and inactivates myosin light chain kinase (MLCK)

describe beta 3 adrenergic receptor signalling

it is located mainly in the adipose tissue (fatty ) which regulates lipolysis

1. NA binds & stimulates the adenylate cyclase which increase cAMP level

2. this activates PKA which stimulates the breakdown of lipids