6-7: aa + Monoamine receptors Flashcards
what are the 3 important amino acids?
glutamate
GABA (gamma amino-butyric acid)
glycine
glutamic acid decarboxylase converts glutamic acid to what?
to GABA!
GLUTAMATE:
- found where? excites (5)
- plays a critical role in (2)
- used to treat what?
- receptors are all __________ –> 2 main types we need to know?
- found everywhere in CNS –> excites cerebral cortex, spinal cord, brain stem, hippocampus, cerebellum
- plays a critical role in long-term potentiation (memory) and neuroplasticity (reforming brain pathways)
- used to treat amyotrophic lateral sclerosis (ALS)
- receptors are all EXCITATORY –> ionotropic: NMDA vs AMPA receptors
(also kainate receptor (ionotropic) and metabotropis (group 1, 2, 3)) - universal excitator!!!
what are the differences btw AMPA and NMDA receptors?
- for which neurotransmitter?
- for glutamate!
AMPA: - Na+ and K+ influx only
- responds to weak stimulation
NMDA: - needs 2 ligands (glutamate + glycine)
- needs electrostatic repulsion to unplug Mg++ block –> IMPORTANT!
*weak stimulation can unlodge Mg –> then Ca2+ can enter –> lots of post-synaptic effect (ie can recruit more AMPA) - Ca++ influx along with Na+ and K+
- what is excitotoxicity?
- which type of receptors are responsible for excitotoxicity and cell death?
- results from excessive stimulation of what? (2)
- BUT these receptors can also contribute to 2 positive things
- conditions linked to excitotoxicity (6)
- trauma!! (associated with glutamate)
- extrasynaptic NMDA receptors!
- results from excessive stimulation of NMDA and AMPA receptors (core memory)
- synaptic NMDA receptors contribute to health and longevity of cells
- stroke, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, spinal injuries
which compound can attenuate NMDA-induced excitotoxicity?
Curcumin! protects neurons from glutamate induced excitotoxicity
TURMERIC (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:
- SCIENTIFIC NAME: Curcuma longa
- PART USED: rhizome (root)
- MODE OF ADMINISTRATION: oral (fresh or boiled, ground)
- BIOACTIVE COMPOUND: curcumin
- COMPOUND CLASS: curcuminoid (phenolic compound)
- USES: anti-inflammatory + antioxidant + boosts BNDF (brain derived neurotropic factor) + Anti-Alzheimer’s (can cross BBB)
GABA = universal what?
- stands for what?
- found where? (2 ish)
- inhibits or activate which parts of nervous system?
- used to treat (3 main categories ish)
- receptors?
- gamma-aminobutyric acid = universal inhibitor!
- found everywhere in CNS + in interneurons
- inhibits cerebral cortex, spinal cord, brainstem, hippocampus, cerebellum, basal ganglia
- anxiety and rehab for drug use (too little GABA = generalized anxiety) + inhibits motor, sensory, cognitive neurons + sedation, muscular/cardiovascular relaxation, inhibits pain and reflexes
- ALL inhibitory! have both ionotropic and metabotropic GABA (A vs B) receptors
GABA receptors have a lot of what? give examples
- plants that affect GABA will be covered in which lecture?
have a lot of PAMs!
- benzos –> benzodiazepine (sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant)
- barbs –> barbituates (CNS depressant, hypnotic, anxiolytic, anticonvulsant, potentially addictive)
GLYCINE
- found where?
- inhibits or activates what?
- used to treat what?
- receptor?
- found only in spinal cord!
- inhibits spinal cord interneurons
- used to treat spasticity
- only ionotropic Cl- channel receptors! no metabotropic
Strychnine
- acts as what? –> result?
- occurs in which part of which scientific plant?
- used to make what?
- act as selective competitive ANTAGONIST to block the inhibitory effects of glycine at the glycine receptors
- occurs in seeds of strychnos nux-vomica (Loganiaceae)
- used to make poison arrows
STRYCHNINE TREE: (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:
- SCIENTIFIC NAME: strychnos nux-vomica
- PART USED: seeds
- MODE OF ADMINISTRATION: inhgestion, inhalation, injection (arrow piercing)
- BIOACTIVE COMPOUND: strychnine
- COMPOUND CLASS: alkaloid
- USES: poison, convulsant
Strychnine poisoning
- strychnine is a what?
- also an agonist/antagonist of which receptors?
- affects what?
- poisoning results in what? –> eventual what?
- glycine receptor antagonist
- antagonist of ACh receptors –> inhibits relaxation
- affects motor nerve fibers (muscles) in the spinal cord –> which control muscle contraction
- poisoning results in muscular convulsions
- eventual death through asphyxia (choking)
- what are the 4 main monoamines?
- why are they called monoamines?
- 2 categories –> examples, synthesized using what? degraded using what?
- serotonin (happiness)
- dopamine (satisfaction, addiction)
- norepinephrine
- epinephrine
*because 1 nitrogen!
1. catecholamines: - dopamine, epinephrine (adrenaline)
- synthesized from tyrosine
- degraded intracellularly by monoamine oxidase (MAO)
2. indolamines: - serotonin
- synthesized from tryptophan
- degraded intracellularly by MAO
AYAHUASCA (monograph)
- SCIENTIFIC NAME:
- PART USED:
- MODE OF ADMINISTRATION:
- BIOACTIVE COMPOUND:
- COMPOUND CLASS:
- USES:
- SCIENTIFIC NAME: banisteriopsis caapi
- PART USED: stems and bark
- MODE OF ADMINISTRATION: decoction (drink it)
- BIOACTIVE COMPOUND: Harmine
- COMPOUND CLASS: Alkaloid
- USES: entheogenic + monoamine oxide inhibitor!
what are the 2 “ingredients” of ayahuasca/to get high? give examples of plants
- MonoAmine Oxidase INHIBITOR!
- ie ayahuasca (banisteriopsis caapi) - Dimethyltryptamine (DMT) containing plants
- chacruna (psychotria viridis), chagropanga (diplopterys cabrerana), jurema preta (mimosa tenuiflora)
- DMT is naturally endogenously produced
OR - non-DMT containing plants (used instead of psychotria)
- water willow (justicia pectoralis), angel’s trumpets (brugmansia), aztec tobacco (nicotania rustica)
- what is the most abundant b-carboline (or harmala alkaloid) in Banisteriopsis caapi?
- what does it do?
- used as what before arrival of what
- Harmine!
- inhibits breakdown of monoamie transmitters (serotonin and dopamine) and hormones (melatonin, epinephrine, NE)
- as MAO inhibitors, harmine can replenish levels of serotonin and dopamine
- MAOis were used as anti-depressants before arrival of selective serotonin receptor inhibitors (SSRIs) in 1987
what is the only known drug to induce proliferation of alpha and beta cells of pancreas of adults?
- how does that drug do so?
- benefit for who?
- harmine! (in ayahuasca)
- inhibits DYRK1A enzyme pathway –> plays a role in suppressing and regulating cell proliferation
- has been found to increase beta-cell mass (produces insulin) in people with type 1 and type 2 diabetes. research as a possible treatment is ongoing
*don’t need to know the details
DMT
- derivative of what?
- responsible for what?
- can we produce DMT endogenously?
- can it be eaten?
N,N dimethyltryptamine
- tryptamine!
- responsible for hallucinogenic properties of ayahuasca (Yagé)
- we may produce DMT endogenously –> our own body’s psychedelic! –> through meditation or by dying…
- DMT CANNOT be eaten –> MAO in the stomach and GI lining metabolize it before entering bloodstream –> it can be prepared as a powdered snuff (have someone blow it into your brain/nose cavity
DMT acts as what? how do we know that?
- can accumulate where?
- acts as agonist of 5-HT receptor (serotonin receptors!)
- serotonin receptors have shown desensitization with repeated exposure to DMT (only 5-HT2C though, not 5-HT2A)
- also acts as agonist of 5-HT1A and increases subjective effects of DMT, suggesting a buffering effect on hallucinogenic effects of 5HT2 receptors
- DMT accumulates in cerebral cortex, caudate, putamen and amygdala (limbic/emotions center!)
serotonin (scientific way of writing ish?)
- found where? (a lot of places)
- used to treat (2)
- receptors?
5-HT
- brain and brainstem: pineal gland, raphe nuclei in pons, limbic function –> emotions, mood, hunger, sex, instincts, temp, sex
- used to treat depression and sleep regulation
- ionotropic (excitory) and metabotropic (excitatory and inhibitor)
SEROTONIN
- most found where in body? where it helps control what?
- produced by which cells?
- what can influence its production and the availability of which aa?
- important axis? thus?
- most found in gut! where it helps control bowel movements
- produced by enterochromaffin (EC) cells lining the digestive tract
- healthy gut bacteria can produce short-chain FA like butyrate that can influence the production of serotonin in enterochromaffin cells –> can also alter availability of tryptophan
- BRAIN-GUT AXIS! more nerves in gut than in spinal cord! link btw depression and IBS is strong –> enteric nervous system!
what does serotonin act as in the
BRAIN? –> regulates (7)
vs GUT? –> regulates (5)
BRAIN: acts as an inhibitory neurotransmitter that regulates
- mood, fear, anxiety
- feelings of relaxation, mental focus, clarity of thought
- learning ability
GUT: acts as a hormonal messenger that regulates
- satiety
- food cravings
- digestion
- nutrient absorption
- peristalsis
*understand, no need to memorize
what happens when you have low serotonin (5) vs normal (2) vs high (2)
*MEMORIZE THIS
LOW:
- depression
- anxiety
- pain sensitivity
- sleep disturbances
- fatigue
NORMAL:
- happiness and relaxation
HIGH
- medical emergency –> death
- causes: SRIs and OTC supplements –> not natural
