week 7- lecture 2 peptides Flashcards Preview

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Flashcards in week 7- lecture 2 peptides Deck (16):
1

peptides overview

-peptides consist of 2 or more amino acids
(note proteins also consist of amino acids but are normally much larger with many more amino acids, Some amino acids are produced in the body others need to be eaten (these are the essential amino acids)
-In the brain most peptides are NOT synthesized from smaller compounds but are the product of larger compounds (poly-peptides) being broken down into peptides within the neuron before release at the terminal button.
-Most peptides serve as modulators, some act as neurotransmitters
Many peptides known to be hormones also act as neurotransmitters and are often co-release with other neurotransmitters….another example of the same compound having multiple roles and different functions in different contexts or brain regions!

2

Peptides - Opioids

Best known family of peptide neurotransmitters are the endogenous opioids

Endogenous Opioids = “originating internally” +“like opium”
Opiates = drugs such as morphine, heroin and opium

3

3 types of opioids

Mu (μ), Kappa (κ) and Delta (δ), are all g-protein coupled and have many different effects
e.g. the Mu receptor is associated with Analgesia, euphoria, sedation, constipation, addiction and hormonal changes
In the brain the highest density of opiate receptors are in areas involved in pain.

4

Peptides - Opiate Drugs

-Opiates are most known for their analgesic (pain relief) and euphoric properties.
-Heroin is highly addictive - not particularly neurotoxic – but can cause death by respiratory failure.
Can destroy your life (or lifestyle) without destroying your brain!!
-Buprenorphine is a partial agonist at the receptors used as a treatment for heroin dependence.
-Naloxone is a full antagonist and can be used to rapidly block the effect of heroin and prevent overdose. -Methadone is also a full antagonist (like Naloxone) and is used in treatment of dependence but much slower time course than Heroin

5

Lipids - Overview

-Naturally occurring molecules that include fats, waxes and many others ….
-They are hydrophobic = “Water Fear”
-Main biological function is energy storage, signaling and provide the structural components of the cell membranes

6

Lipids - Endocannabinoids

-In the brain the best known lipid neurotransmitters are the endocannabinoids (“endogenous cannabis-like substances”).
-2 known cannabinoid receptors CB1 & CB2 - Both are G-protein receptors.
-CB1 is found in the brain and is believed to be responsible for the main psychological effects (CB2 is found in peripheral tissue).
-CB1 receptors found on terminal buttons of
Neurons that release most of the major
neurotransmitters/modulators.
-CB1 receptor activation >> shortens the duration
of action potentials in the presynaptic neuron >>
decreasing amount of neurotransmitter released
-By regulating the activity of those neurons and
release of neuromodulators these receptors
act to modulate the modulators!!!

7

Lipids – Cannabis/Marijuana

-THC (tetrahydrocannabinol) is the active compound in marijuana.
-The plant is dried and consumed by inhalation
-Effects range from changes in appetite, time perception, arousal (relaxation/anxiety) ..
-Therapeutically used to reduce nausea, relieves asthma attacks, decreases pressure within the eyes in glaucoma.
and have also been linked to states of apathy and “underachievement

8

Nucleosides - Overview

-Nucleoside are a subunit of nucleic acids, the heredity-controlling components of all living cells – such as DNA & RNA
-Nucleosides are usually obtained by chemical/enzymatic breakdown of nucleic acids and consists of a molecule of sugar linked to a nitrogen-containing compound.
Often “co-transmitters” that serve to modulate the release of other transmitters.. Again modulating the modulators
One example of a nucleoside is Adenosine

9

Nucleosides - Adenosine

-Adenosine in the brain is an inhibitory neurotransmitter.
-It is a nucleoside that forms from the breakdown
of adenosine triphosphate (ATP). ATP is the
primary energy source in cells for transport
systems and many enzymes.
-When you are awake adenosine levels gradually
rise and in normal conditions it promotes sleep
and suppresses arousal.
-At synapses where adenosine is the primary
neurotransmitter, a high postsynaptic firing
rate leads to sleepiness. An example where
“increased firing = reduced activation/arousal.”
-Adenosine in the body decreases heart rate and causes blood vessels to dilate and also has a range of effects in the kidneys, lungs and liver

10

Nucleosides - Caffeine

-Occurs naturally in plants: e.g. coffee beans, cacao beans & tea
-For plants, caffeine acts as a natural pesticide that paralyzes and kill insects that attempt to feed on the plants.
-Over 400 billion cups of coffee consumed a year….
-Acts as adenosine-receptor antagonist and blocks the natural action of adenosine
-because adenosine increasing firing rate in brain areas that promote sleepiness, caffeine increases alertness by reducing the firing/activation of these neurons.
VERY Different to other true stimulant drugs like cocaine!!


11

Gases - Overview

-Gas = air-like fluid substance which expands freely to fill any space available, irrespective of its quantity.
-Soluble gases: dissolve in fluid
(dependent on pressure & temperature)
Recently discovered that neurons use two gasses as neurotransmitters: nitric oxide and carbon monoxide.



12

Gases – Nitric Oxide

Nitric oxide (NO) was named “molecule of the year in 1992” and was the topic of the Nobel Prize in Physiology or Medicine 1998
“For discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system”
… and Viagra

13

Gases – Nitric Oxide (NO)

In the brain NO is produced from the amino acid Arginine

by the enzyme Nitric Oxide Synthase (NOS) which is found in a subpopulation of 1-2% of neurons in cortex.

14

NOs role in the brain

NO’s exact function role in the brain is unclear
-It is involved in learning and memory through effects on synaptic plasticity
-It dilates blood vessels in regions of the brain that become metabolically active

15

NO is very different to traditional neurotransmitters.

-NO is not synthesized and stored in vesicles like other neurotransmitters.
-NO is produced throughout the cell including dendrites and defuses out of the cell as soon as it is produced.
-NO does not activate receptors but simply enters the neighboring cell
-NO is very short lived and is degraded or reacted within a few seconds of being produced
-It can act on several nearby neurons, even on those not connected by a synapse. However, NO’s short half-life means that its action will be restricted to a limited area, without the necessity for enzymatic breakdown or cellular reuptake.

16

Summary

-Peptides: 1 major class is the opioids which are important in pain relief. Opiate drugs are effective but are also highly addictive
- Lipids: The cannabinoid receptors are found near the synapses of most neurons that release neurotransmitters where they act to modulate the modulators.
-Nucleosides: Adenosine activation increases drowsiness. Caffeine promotes wakefulness through inhibition of this response
-Gasses: Nitric Oxide was only recently discovered and highlights the range of molecules that can act as neurotransmitters