Lecture 3: Plants that affect acetylcholine receptors Flashcards
Organs and glands activated by the sympathetic nervous system
brain, muscles, the pancreas, thyroid gland and adrenal glands
Organs and glands affected by the parasympathetic gland
the liver, kidneys, pancreas, spleen, stomach, small intestines and colon
Hormones and substances elevated by the sympathetic nervous system
insulin, cortisol, and the thyroid hormones
hormones and substances elevated by the parasympathetic nervous system
pancreatic enzymes, bile and other digestive enzymes
types of amino acid neurotransmitters
Glutamate, GABA, Glycine
types of monoamine neurotransmitters
- Indolamines: Serotonin (a hormone, NOT a NT)
2. Catecholamines: Dopamine, Norepinephrine, Epinephrine
type of purine neurotransmitter
Adenosine
type of peptide neurotransmitter
Opioid
Where is acetylcholine found
1) motor neuron
2) brain
3) autonomic nervous system
- sympathetic: Ganglion NT
- parasympathetic: Both ganglion and terminal
Function of acetylcholine
a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system.
Acetylcholine receptors
1) ionotropic: nicotinic receptors
2) metabotropic: muscarinic receptors
nicotinic receptors vs. muscarinic receptors
nicotinic: opens very simple and fast. Ligand binds - open - response
muscarinic: ligand - conformational change - activation of G protein subunits - release of secondary messengers - response
Tobacco scientific name(s)
1) Nicotiana rustica (Aztec tobacco)
2) Nicotiana tabacum
Tobacco - parts used
Leaves
Tobacco - Bioactive compound
Nicotine
Nicotine mechanism
- acts as a receptor agonist at a a7 nicotinic acetylcholine receptor
- it may also function by inhibiting acetylcholinesterase
- a7 directly stimulates the acetylcholine recptors on dopamine - containing neurons and cause an overflow of dopamine
- it also activates the sympathetic nervous system, stimulating the release of epinephrine
what are PAM(s)
they are called positive allosteric modulators - other things required for the agonistic binding of nicotine and nicotinic acetylcholine receptors
development of nicotine addiction
1) Craving - no nicotine in the bloodstream
2) Cigarette - in the presence of nicotine, the receptor opens and lets the signal through
3) cigarette just finished - the receptor is desensitized and does not respond to more nicotine
4) long term smoking increases craving - more receptors are formed with long term exposure to nicotine, to increase sensitivity.
tobacco and cancer/atheroscelrosis
- curing and aging tobacco leaves generates carcinogenic tobacco-specific nitrosamines (TSNAs)
- starch is then converted to sugar, which glycates proteins; this oxidizes into advanced glycation end-products (AGEs)
- Inhalation of AGEs is a major contributor to atherosclerosis and cancer
Insufflation
the act of blowing something onto a body cavity
expectorant
promotes the secretion of sputum (a mixture of saliva and mucus coughed up from the respiratory tract)
Ethneogenic
a drug that causes one to become inspired or to experience feelings of inspiration, often in a religious or spiritual manner
Fly Agaric - scientific name
Amanita muscaria
Fly Agaric - part used
Entire mushroom
Fly Agaric - bioactive compound
Muscarine
Function of muscarine
- mimics the action of Ach on muscarinic acetylcholine receptors
- Causes profound activation of the parasympathetic nervous system
- not degraded by acetylcholinesterase
- can cause circulatory collapse and death
Treatment of muscarine toxicity
Atropine - a competitive reversible antagonist of muscarinic receptors
Muscimol
Cause of hallucinations and toxicity - it is a potent selective GABA a receptor agonist
- responsible for the drunkenness, sedative, depressant, euphoric and dissociative effect
Ibotenic acid
cause of hallucinations and toxicity
- potent agonist of the NMDA (N-methyl-D-aspartate) metabotropic glutamate receptors.
- responsible for nausea, stomach cramps ad vomiting associated with Amanita ingestion
main psychoactive compounds of Amanita muscaria
muscimol and isotonic acid
Divination
represents a way to induce deep concentration and introspective thought
name the plants used for divination with their scientific name and main compounds
1) Angel’s trumpets: Brugmansia spp. ; tropane alkaloids: scopolamine, hyoscyamine, atropine
2) Jimoson weed: Daturam stramonium; tropane alkaloids: scopolamine, hyoscyamine, atropine
3) morning glory: Ipomoea tricolor; ergo line alkaloids: ergonovine, ergine
Jimson weed - scientific name
Datura stramonium
Jimson weed - parts used
Seeds/leaves
Jimson weed - bioactive compounds
Atropine, hyocamine, scopolamine
Fate of acetylcholine after being broken down by acetylcholinesterase
Choline is transported back into the axis terminal and is used to make more Ach
Anticholinergic Toxidrome
results from competitive antagonism of acetylcholine at central and peripheral muscarinic receptors
Anticholinergic Toxidrome symptoms
confusion dry mouth urinary retention shaking dilated pupils (mydriasis) flushed skin absent bowel sounds tachycardia hyperthermia
Anti-cholinergic
inhibits the transmission of the NT acetylcholine and suppress the parasympathetic nervous system
anti-cholinergic substances can cause:
amnesia, bizarre behaviour, and the inability to distinguish reality from fantasy (hallucination)
tropane alkaloids are ——-
anti-cholinergenic
examples of anti-cholinegernic substances
1) atropine
2) scopolamine - used to treat motion sickness and post-operative nausea
3) hyoscyamine - provides symptomatic relief of spams caused by peptic ulcers, IBS, pancreatitis, and colic
Glycoalkaloids
- what are they
- mechanism
natural pesticides found in high concentration in leaves, flowers, and unripe fruits
mechanism: they bind strongly to cholesterol in cell membranes causing cells to leak or burst open; also block acetylcholinesterase: lead to paralysis, convulsions, respiratory arrest, and death
Solanine
the alkaloid attacked to glucose chains (glycoalkaloid)
poorly absorbed by the gut and causes GI irritation.
Solanine and tomatine - anti-cancer activities
solanine: alpha solanine has anti-proliferation and an apoptosis promoting effect on multiple cancer cels
tomatine: binding of tomatine to cholesterol may be the mechanism of inhibition of carcinogenesis.
Chili pepper - scientific name
Capsicum annuum
Chili Pepper - part used
fruit
Chili pepper - bioactive compound
Capsaicin
Glutamate receptor
- excites the cerebral cortex, spinal cord, brain stem, hippocampus, cerebellum
- plays a critical role in long term potentiation (memory) and neuroplasticity
Glutamate receptors types
1) ionotropic: NMDA, AMPA, Kainate
2) metabotropic: Group 1,2,3
AMPA vs. NMDA receptors
1) AMPA: needs only one ligand (glutamate) and there is only a Na and K influx
2) NMDA: needs 2 ligands (glycine+glutamate); needs electrostatic repulsion to unplug Mg block (charges it), Ca Na and K influx
- in both cases, Na goes in and K goes out of the membrane
Excitotoxicity and cause
results from excessive stimulation of EXTRA-SYNAPTIC NMDA and AMPA receptors
conditions linked to excitotoxicity: stroke, traumatic brain injury, MS, Alzheimer’s, spinal injuries
Synaptic vs. extra synaptic NMDA receptors
extra-synaptic: responsible for excitotoxicity and cell death
synaptic: contribute to health and longevity of cells
Curcumin and extra-synaptic NMDA receptors
Curcumin attenuates NMDA-induced excitotoxicity
Turmeric -scientific name
Curcuma longa
Turmeric - part used
rhizome
turmeric - bioactive compound
curcumin
GABA - location and function
found in interneurons and everywhere in the CNS
inhibited the cerebral cortex, spinal cord, brainstem and hippocampus
GABA - treatment uses
1) anxiety and rehab - too little GABA can cause generalized anxiety
2) inhibits motor, sensory and cognitive neurons
3) sedation, muscular/cardiovascular relaxation, inhibits pain, reflexes
GABA receptors
1) ionotropic: GABAa
2) metabotropic: GABAb
GABA a function
- helps increase intracellular Cl ions
- contains: 2 subunits of GABA, barbiturates, benzodiazepine and channel for Cl influx
“Benzos”
- a class of psychoactive drug
- sedative
- hypnotic
- anxiolytic
- anti-convulsant
- muscle relaxant
“Barbs”
- a class of psychoactive drug
- potentially addictive
- CNS depressant
- Hypnotic
- Anxiolytic
- Anti-convulsant
Glycine receptors - location
found in the spinal cord
Glycine - function
inhibits spinal cord interneurons (same impact as GABA but mostly in the spinal cord)
Glycine - treatment use
spasticity (abnormal increase in muscle tone and stiffness)
glycine receptors
1) ionotropic: Cl channel
glycine receptor and strychnine:
receptor can be selectively blocked by the high-affinity competitive antagonist strychnine.
- selective competitive antagonist of glycine
where is strychnine made
in the seeds of strychnos nux-vomica (Loganiaceae)
Strychnine tree - scientific name
strychnos nux - vomica
strychnine - parts used
seeds
strychnine mode of administration
ingestion, inhalation, injection
Monoamine neurotransmitters
- serotonin
- dopamine
- norepinephrine
- epinephrine
Catecholamines
- examples
- precursor
- degradation
epinephrine and dopamine
- tyrosine
- degraded intracellularly by monoamine oxidase
Indolamine
- example
- precursor
- degradation
- serotonin
- tryptophan
- degraded intracellularly by monoamine oxidase
Ayahuasca - scientific name
Banisteriopsis caapi
Ayahuasca - part used
stems and bark
Ayahuasca - bioactive compound
Harmine
The most abundant beta-carboline in B.caapi is ——
Harmine
function of Harmine
1) inhibits the breakdown of monoamine transmitters (serotonin, dopamine) and hormones (melatonin, epinephrine, norepinephrine)
- as monoamine oxidase inhibitors, carmine can replenish levels of serotonin and dopamine - used to be utilized as an antidepressant
2) causes proliferation of alpha and beta cells of the pancreas
- inhibits the DYRK1A enzyme pathway - suppressing and regulating cell proliferation
- increase beta cell mass in people with type 1 and type 2 diabetes *
ingredients for preparation of Ayahuasca that cause hallucination
- DMT containing plants
e. g. Charcuna, Chagropanga, Jurema preta
Non - DMT containing plants that are used for the preparation of Ayahuasca (used instead of Psychotria)
- water willow (Justicia pectoralis)
- Angel’s trumpets ( Brugmansia)
- Aztec tobacco (Nicotania rustica)
DMT is a derivative of ——
tryptamine
DMT is responsible for:
hallucinogenic properties of Ayahuasca
DMT in the body
monoamine oxidase in the stomach metabolize it before entering the blood stream
DMT mechanism of action
- acts as an agonist of 5-HT2a and 5-HT2c receptor
The 5-HT2c shows desensitization with repeated exposure to DMT (no 5-HT2a) - also and agonist at 5-AT1a and increases the subjective effects of DMT, suggesting a buffering effect on the hallucinogenic effects of 5-HT2c
- accumulates in the cerebral cortex, caudate, putamen, and amygdala
Serotonin - location
found in the brain and brainstem
Serotonin - treatment
1) depression
2) sleep
receptors of serotonin
1) ionotropic: 5H3 (excitatory)
2) metabotropic: 5HT (1-7 receptors) - can be both excitatory or inhibitory depending on the tissue
serotonin is produced by —— in the ——.
How:
enterochromaffin (EC) cells , digestive tract
- gut bacteria produce short chain fatty acids like butyrate that can influence the production of serotonin
why is the link between depression and IBS strong
due to the brain gut axis
there are lots of nerves in the gut
Functions of serotonin in the Brian
acts as a NT that regulates:
1) mood
2) fear
3) anxiety
4) feelings of relaxation
5) mental focus
6) learning ability
7) clarity of thought
Functions of serotonin in the gut
acts as a hormonal messenger that regulates:
1) satiety
2) food cravings
3) digestion
4) nutrient abs
5) peristalsis
Ergot - scientific name
Claviceps purpurea
Ergot - parts used
Sclerotium
Ergot - bioactive compound
ergotamine
Ergotism - cause
ingestion of sclerotia of the parasitic fungus Claviceps purpurea
Ergotism - types
1) serotonergic stimulation of CNS - muscle spams, fever and hallucinations
2) Vasoconstriction of the vascular system - violent burning, absent peripheral pulses and shooting pain of the poorly vascularized vital organs
Morning glory - scientific name
Ipomea tricolor
Morning glory - parts used
seeds
Morning glory - bioactive compound
Ergine
LSD - affects
causes altered thoughts, feelings, hyper awareness, dilates pupils, increases blood pressure and body temperature
how are ergot alkaloids serotogenic
- similar structure to serotonin, dopamine, and epinephrine. can being to several receptors and acts as an agonist
how do ergot alkaloids cause vasoconstriction
through the stimulation of the alpha - adrenergic receptors.
Inhibits the uptake of norepinephrine
How to raise serotonin levels naturally
Foods ( carbs increase tryptophan transport across the bloodstream-brain barrier) Exercise (release tryp in to the blood) Bright light mooD and mindset Massage Probiotics
St. John’s Wort - scientific name
Hypericum perforatum
St. John’s Wort - parts used
Flowers and buds
St. John’s Wort - bioactive compound
Hyperforin and Hypericin
St. John’s Wort - complication
photosensitivity
potential function of hyperforin
displays a similar activity to other selective serotonin reuptake inhibitors (SSRIs) and with better tolerance
- helps with depression
St. John’s Wort mechanism in relationship to drugs
induces the cytochrome p450 enzymes: CYP3A4 , CYP1A2
This increases the metabolism of certain drugs; thus, decreased clinical effects and plasma concentration
