W3 Flipped lecture content Flashcards
Acetylcholine acts on what?
Nicotinic (iontropic and muscarinic metabotropic) receptors.
Acetycholine
created by combined acetyl and choline. Acetylcholine Destroyed in the synaptic cleft by an enzyme. Choline is recycled to make more acetylcholine.
ChAT = good marker for cholinergic neurons.
Acetyl CoA
Nicotinic (nAChRs):
ACh-gated Na+/Ca2+ channel, found at neuromuscular junction, CNS.
Muscarinic (mAChRs)
5 types of GPCRs, found in CNS and autonomic nervous system. Recall Loewi’s 1921 experiment on the heart: the ‘vagusstoff’ was ACh!
Neutroasmitter at the neuromyscluar junction (NMJ)
Acetylcholine used as a neuromusclar hunction, NMJ motor nerve excites the muscle.
- Block release [Acetylcholine: pharmacology]
- Block release (paralyzing you).
Botulinum towin (produced by bacteria),
Black widow spier venom (first increases ACh release at NMJ then elminates it. Seems to work by allowing a big calcium influx)
Acetylcholine: pharmacology
- Block release
- Block AchE
- Activate ACh Receptors
- Block ACh receptors
Block AchE [Acetylcholine: pharmacology]
Nerve gas
Organophosphate pesticides
Alzheimer’s treatments
- Activate ACh receptors [Acetylcholine: pharmacology]
Nicotine, muscarine
Neonicotinoid pesticides
Block ACh receptors [Acetylcholine: pharmacology]
Nicotinic (curare)
Alpha bungarotoxin from snake venom binds to nAChRs and takes days to unbind
Bungarus multicinctus, alpha-bngarotoxin
Muscarinic: atropine
Monoamines are synthesised from what?
Amino acids.
Epinephrine
Adrenaline, named after the adrenal gland
Storage adn removal of monamines
Pached into vesicles by vesicular monoamine transporters (VMAT)
Removed from the synaptic cleft by re-uptake transporters
Destroyed by monoamine oxidase (MAO) and catechol-O-methyltransferase
What are the epinephrine, norepinephrine receptors
Adrenergic recpeotrs; alpha and beta types
Different receptors
activate different Gprotein effectors. Different receptors are expressed in different neuron types or parts of the brain. That’s why drugs can have specific effects.
Dopamine Motor control
Dopaminergic neurons in the substantia nigra prokect to the striatum. This nigrostriatal pathway facilitations initiation of voluntary movement. These neurons die in PD = motor dysfunction
How can PD be trated
Increasing dopamine.
TH is rate-limiting in synthesis of dopamine, so can give L-DOPA (dopamine doesn’t cross the blood-brain barrier
The loss of the dopaminergic neurons causes the motor symptoms.D
Dopamine - Reward
Dopaminergic neurons in the ventral tegmental area (VTA) prokect to the cortex and limbic system. This mesolimbic pathway mediates ‘reawrd’/’motivation’
Cocaine, amphetamines
Block reuptake of dopamine, norepinehrine
Antipsychotics
Block dopamine receptors (parkinson’s like symptoms (possible side effect))
Antidepresents
-tricyclics: block reuptake of NE, serotonin
-selective serotonin reuptake inhibitors (SSRIs), e.g. fluoxetine (Prozac)
-MAO-A inhibitors
Opinoid peptides (endorphins)
Bind to opioid receptors (GPCRs)
Regulate pain (perception/emotion/cognitive)
Also regulate coughing, GI tract.
Opioid receptors are the targets of morphine, heroin.
ATP
often a co-transmitter
Nitric Oxide
Gas, membrane-permeable
Acts on soluble guanylate cyclase, not a membrane receptor
Endocannabinoids
Lipid-soluble, not in vesicles
Ca2+ triggers synthesis, not vesicle fusion
Retrograde signaling (postpre)
Bind to GPCRs (the targets of the active compound in cannabis)
