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Neurotransmitter release is dependent on
Calcium
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All neurotransmitters have what traits
They are small water soluble molecules
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Excitatory neurotransmitters increase the permeability to what
Sodium and sometimes calcium
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Inhibitory neurotransmitters increase permeability to what
Chloride or potassium hyperpolarizing the cell
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What are the two types of neurotransmitter receptors
- G-protein linked receptors (slow)
- Ligand gated ion channels (fast)
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Adrenergic, dopamine, muscarinic, cholinergic, and opiate receptors are examples of what type of receptors
G-Protein
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Nicotinic cholinergic, GABA-A, and NMDA are examples of what type of receptors
Ligand gated
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Acetyl-CoA + Choline =
Acetylcholine
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Choline used to make acetylcholine is found where in abundance
It occurs in membrane lipids like Phosphatidylcholine and sphingomyelin and is thus readily available
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How are the ion channels opened
They contain a binding sight for acetylcholine (or other neurotransmitters) and when they bind they open the channel
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What attracts the ions to the ion channels
They have a negative charge close to the gate
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Why does sodium pass through the ion gates more readily then the potassium
The sodium has a larger electrochemical gradient
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Nicotinic receptors
Ligand gated sodium channels in neuromuscular junctions, autonomic ganglion, and the brain
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Muscarinic receptors
G-protein linked receptors froming IP3 or lowering cAMP in parasympathetically innervated tissues, sweat glands, and the brain
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Curare
Drug that blocks Nicotinic receptors in the neuromuscular junction, indians used them in their arrows
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Atropine and Scopolamine are drugs with what effect
They block Muscarinic receptors
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Organophosphates are drugs that have what effect
- They inhibit acetylcholinesterases irreversibly by reacting with the serine residue in its active site
- Used in pesticides and chemical warfare
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Tyrosine can be made into what Biogenic amine (neurotransmitter) by what reaction
- Catecholamine through decarboxylation
- "Run the Cat over with a Tyre"
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Histamine is a biogenic amine made by what process from what amino acid
Decarboxylation from Histidine
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Indoleamines are biogenic amines that are made from what amino acid
Tryptophan via decarboxylation
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Serotonin is an Idoleamine with a technical name of
5- Hydroxytryptamine (5-HT)
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What is the sequence of molecules made in Catecholamine synthesis
- Tyrosine
- L-DOPA
- Dopamine
- Norepinephrine
- Epinephrine
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How is the inactivation of Catecholamines in the synaptic cleft different from other neurotransmitters
They have to first be taken back up into the nerve terminal before they are broken down
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How are Catecholamine's taken back up into the nerve terminal
Sodium Co-transport
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The deamination and subsequent methylation of Catecholamines in the presynaptic cell happens how
MAO (deamination) and then COMT (methylation)
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The uptake of Catecholamines can be manipulated by drugs because
It is taken up by a sodium co-transport, restricting the build up of sodium via ATP pumps can be regulated or stopped by drugs slowing down the uptake of catecholamines for breakdown
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The inactivation of Norepinephrine can happen via what routes
MAO and then COMT vice verse
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What is the harmful product made by the break down of Norepinephrine
H2O2 Hydrogen peroxide which can make free radicals
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Serotonin and subsequently Melatonin are made via what sequence of formed molecules
- Tryptophan
- 5-Hydroxytryptophan
- 5-HT (Serotonin)
- Melatonin
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What is the effect of Melatonin
It is used as a sleep aide and is found only in the Pineal gland in the brain
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A deficiency in Vit B6 can have what effect
It can cause difficulty in making neurotransmitters specifically Seritonin, Melatonin, Norepinephrine, and Epinephrine
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Serotonin (5-HT) is broken down via what pathway
- Uptake into the nerve terminal
- Oxidative Deamination by MAO
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The breakdown of Biogenic amines (Dopamine, Epinephrine, Serotonin) is removed by what process
Urine
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Dopamine is broken down to what for removal
Homovanillic acid
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Epinephrine and Norepinephrine is broken down to what for removal from the body
Vanillylmandelic acid
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Serotonin is broken down to what for removal from the body
5-Hydroxyindoleacetic acid
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What are the MAO's for 5-HT, and Dopamine respectively
- MAO-A "Sera (Serotonin) always gets A's"
- MAO-B "Moab is Dope!"
- Norepinephrine is degraded by both
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What is a clinical use of MAO inhibitors
Antidepressants
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What can be the side effects of taking MAO inhibitors
A hypertensive crisis can occur if taken with cheese or red wine. This is because MAO's in the liver breakdown harmful substances in these foods
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Parkinsons disease is caused by what
Degeneration of nigro-striatal Dopamine neurons in the brain
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Why is L-DOPA administration not the preferred method for the treatment of Parkinsons disease
It bypasses the rate limiting step increasing the hydrogen peroxide production which is believed to accelerate the conditions
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Why isn't Dopamine administered directly to Parkinsons diseased patients
It would be broken down by the MAO's in the liver and therefore not have any effects
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Tricyclic antidepressants have what effects
They inhibit the high affinity uptake of Norepinephrine and 5-HT therefore leaving them in the junction longer
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Serotonin-specific reuptake inhibitors (SSRI's) have what effect
They inhibit the high-affinity uptake of 5-HT only
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Cocaine and Methylphenidate have what effect
They inhibit the uptake of Dopamine, Norepinephrine, and 5-HT
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What are the effects of Amphetamines
They release more Dopamine, 5-HT, and Norepinephrine from nerve terminals
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Peptide neurotransmitters are most commonly used where
In short interneurons and are usually released together with other neurotransmitters
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What are the most common peptide neurotransmitters
Endorphins, TRH, Cholecystokinin, and Substance P
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What are the most important neurotransmitters in the CNS and why
- Amino acids
- They have a high affinity re-uptake
- No biosynthetic or inactivating enzymes are needed
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What are the most important amino acid neurotransmitters
- Glutamate, Aspartate (excitatory)
- Glycine (inhibitory)
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Enhanced GABA has what effect in the brain
- Sedative
- Hypnotic
- Anxiolytic (reduce anxiety)
- Anti-convulsant effects
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What are the most important GABA drugs
- Barbiturates (stimulate the GABA-A receptor)
- Benzodiazepines aka. Valium (Sensitize the GABA-A receptors)
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Beta receptors have what effect
- Raise cAMP
- "Beta was raised in a concentration cAMP"
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Alpha 1 receptors have what effect
Activate the IP3 system
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Alpha 2 receptors have what effect
Reduce cAMP
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