Acetylcholine Receptors Flashcards
Where does cholinergic neurotransmission occur?
- neuromuscular junctions
- CNS
- autonomic nervous system
TRUE or FALSE: cholinergic neurotransmission occurs at…
- ganglionic neurons of the sympathetic and parasympathetic
- preganglionic neurons of the sympathetic branch
FALSE:
- preganglionic neurons of the sympathetic and parasympathetic branch
- ganglionic neurons of the parasympathetic branch
Which neurotransmitters are released in the parasympathetic branch, and in what order?
CNS (preganglionic neuron) –> ACh –> parasympathetic ganglion –> ACh –> target organ
Which neurotransmitters are released in the sympathetic branch, and in what order?
CNS (preganglionic neuron) –> ACh –> sympathetic ganglion –> NOREPINEPHRINE –> target organ
TRUE or FALSE: both preganglionic and ganglionic neurons in sympathetic and parasympathetic nervous systems release ACh
FALSE: sympathetic ganglionic neurons release norepinephrine
Agonists of muscarinic receptors are ______________.
parasympathomimetic
Antagonists of muscarinic receptors are __________________.
parasympatholytic
What is meant by parasympathomimetic?
drugs that mimic effects of activation of the parasympathetic nervous system
What is meant by parasympatholytic?
drugs that inhibit parasympathetic functions
What is the striatum involved in?
motor function
What is the dorsolateral pons involved in?
arousal and addictions
What is the basal forebrain cholinergic system (BFCS) involved in?
learning, memory, and attention
Where are cholinergic neurons located in the BFCS?
- medial septum
- diagonal band nuclei
- nucleus basalis
- substantia innominate
Where does the BFCS project to?
cortex, hippocampus, amygdala
What is loss of BFCS cholinergic neurons associated with?
cognitive decline in AD
What kind of drug is atropine? Which receptor does it affect? Is it an agonist or antagonist?
- plant alkyloid found in the nightshade plant
- antagonist of the muscarinic ACh receptor
How is atropine administered?
opthalamologically to dilate pupils
TRUE or FALSE: atropine dilates the pupils
TRUE
TRUE or FALSE: atropine is a parasympathomimetic
FALSE: parasympatholytic
TRUR or FALSE: atropine is BBB permeable
TRUE
What occurs in animals when atropine is orally administered?
inhibit cognition (acquisition and maintenance of learning tasks)
How does atropine affect cognition in humans?
amnesiac
Which drug is closely related to atropine and has an amnesiac effect in humans?
scopolamine
Which drug combination was often administered during labour in the early-mid 20th CE?
scopolamine and morphine
ACh thought to be important for ______________ due to innervation of the hippocampus.
memory consolidation
TRUE or FALSE: using microdialysis, researchers showed that ACh levels decreased during tasks requiring sustained attention.
FALSE: ACh levels increased
using microdialysis, researchers showed that ACh levels increased during tasks requiring ________________.
sustained attention
What is an operant control task?
reward task (e.g. lever press for food reward)
What is a F19-s schedule of reinforcement?
operant reward task with a predictable delay
What is saporin? Is it water soluble?
- protein toxin isolated from soapwort plant
- water soluble toxin
What is the function of saporin?
- highly specific inhibitor of ribosome function (ribosome inactivating protein - RIP)
- can be conjugated to antibodies to target specific cell types (investigated as anti-cancer agent)
What is 192-IGG saporin? What does it target?
conjugated to an antibody that targets basal forebrain cholinergic neurons
What is the result of administering 192-IGG saporin to the ventricular system?
targeting of BFCS neurons neurons and SELECTIVE LESION of only the CHOLINERGIC NEURONS
What does lesion to the BFCS lead to?
deficits in learning, memory (spatial), and attention
In sustained attention tasks animals lesioned with 192 IgG-saporin had a _____ number of correct hits when the signal strength was weak, suggesting ________________.
- lower
- deficits in attention
Cholinergic projections from which brain structure are active while awake?
pons (pedunculopontine nucleus and laterodorsal tegmental nucleus)
how do cholinergic projections from the pons affect sleep?
trigger the transition to REM sleep
Besides cholinergic projections from the pons, what else is also involved in increasing attention?
reticular activation
cholinergic neurons originating in the dorsolateral pons innervate the ______________
ventral tegmental area
cholinergic neurons originating in the _____________ innervate the ventral tegmental area
dorsolateral pons
ACh stimulates ___________ neurons projecting to the nucleus accumbens
dopaminergic
__________ activates nicotonic ACh receptors to directly activate __________. neurons in the VTA.
nicotine, dopaminergic
What are the 2 families of cholinergic receptors found in mammals?
- nicotinic receptors (NAChR)
- muscarinic receptors (MAChR)
How many varieties of nicotinic receptors are there? What kind of receptors are they?
- 17 varieties
- ionotropic receptors pass Na+ and Ca2+
How many varieties of muscarinic receptors are there? What kind of receptors are they?
- 5 varieties
- metabotropic receptors (GPCRs)
What are NAChR permeable to?
Na+ and Ca2+
___________ is a selective agonist of NAChR.
nicotine
Where are NAChR located?
- NMJ
- sympathetic nervous system
- parasympathetic nervous system
- central nervous system
Agonists that do not readily desensitize receptors cause a _________________.
depolarization block
What is the function of a depolarization block?
prevent target cell from firing by preventing repolarization
Under normal circumstances, what occurs to NAChR in the presence of a prolonged stimulus?
desensitization (inactivation)
What is succinylcholine? Which receptor does it affect, and how does it affect the receptor? What symptoms present?
- muscle relaxant
- prolong activation of NAChR
- muscle paralysis
TRUE or FALSE: at the NMJ, NAChR are located both pre and post synaptically
FALSE: at NMJ, only post-synaptic
TRUE or FALSE: in the CNS, NAChR can be located in both post and pre-synaptic membranes
TRUE
What is the function of pre-synaptic NAChR?
modulate neurotransmitter release
What is classic transmission?
receptors located post-synaptically
NAChR antagonists include ___________ (______________).
curare poison, D-tubocurarine
What kind of plants produce curare poison? What was it originally used for?
- tropical plants indigenous to South America
- used as an arrow poison for hunting (causes respiratory paralysis)
ACh is a major neurotransmitter in what organism?
insects
TRUE or FALSE: neuronal NAChR have the same composition and sensitivity in mammals and invertebrates
FALSE: different in mammals and invertebrates
What are neonicotinoid insecticides? Do they have low or high adverse effects in mammals? are they permeable to the BBB?
- irreversible NAChR antagonist
- broad spectrum insecticide
- low adverse effects in mammals
- BBB impermeable
How many types of muscarinic receptors are there?
5 types (M1 through M5)
TRUE or FALSE: muscarinic receptors are metabotropic
TRUE
Is muscarine an agonist or antagonist of muscarinic receptors.
agonist
Where is muscarine isolated from?
fly agaric mushroom
TRUE or FALSE: muscarine is parasympatholytic
FALSE: parasympathomimetic
Ingestion of muscarine leads to exaggerated ____________ response.
parasympathetic
What symptoms arise when muscarine is ingested?
- lacrimation
- sweating
- salivation
- pinpoint pupils
- sever abdominal pain (strong contraction of smooth muscles and painful diarrhea)
What do high doses of muscarine lead to?
cardiovascular collapse, convulsions, coma, death
What is the structure of GPCR?
7-transmembrane helix receptor
GPCR is coupled to specific ________ binding protein on the __________ side.
GTP, intracellular
What is the function of Gs α?
stimulates downstream targets
What is the function of Gi α?
inhibits downstream targets
What is the function of Gq α?
modulatory functions downstream
GPCR elici effects on target cells through ____________, such as ____, _____, and ______.
second messengers, cAMP, IP3, Ca2+
Describe the events of GPCR binding.
- GPCR binds ligand, interacts with G-protein complex
- G-protein complex - Gα binds GDP, Gβ-γ
- ligand binding promotes dissociation of Gα from Gβ-γ
- newly liberated Gα activates downstream effector (e.g. adenylate cyclase –> generates cAMP)
Describe the Gq α/PLC signalling cascade.
- PLC activation cleaves PIP2 (membrane phospholipid) to IP3 (soluble) and DAG (lipid)
- IP3 activates Ca2+ channels on the ER to trigger Ca2+ release into the cytoplasm
- DAG activates protein kinase C in conjunction with Ca2+
- PKC phosphorylates numerous cellular proteins
Describe the events of M1,3,5 binding. Which G protein is it associated with?
M1,3,5 –> Gqα –> PLC –> IP3 and Ca2+ release
What is M1 specifically involved in?
neurotransmission in autonomic ganglion cells (both sympathetic and parasympathetic) and cognitive effects in CNS
What is M5 specifically involved in?
addictive behaviour
Describe the events of M2,4 binding. Which G protein is it associated with?
M2,4 –> Giα –> inhibit adenylate cyclase –> decrease cAMP levels
What is M2 specifically involved in?
- M2 is expressed in the heart
- activation slows heart rate
What is M4 specifically involved in?
- functions as an autoreceptor
- activation inhibits presynaptic ACh release
Which 2 NTs are in balance to regulate movement? Where does this occur?
- ACh and dopamine
- striatum
Degeneration of ___________ neurons in the ____________ results in deficits in initiation of movement.
dopaminergic; substantia nigra
What kind of drugs are used in early PD to treat motor symptoms? What is the rationale?
- cholinergic drugs
- manipulation of ACh in the striatum offsets the deficit in dopamine
What is orphenadrine used for? What kind of drug is it?
- used to treat early PD to treat motor symptoms
- muscarinic M4 ACh receptor antagonist
How does latrotoxin affect ACh?
trigger ACh release
How does botulinum toxin affect ACh?
block ACh release
192 IgG saporin is a ________ __________ toxin.
selective cholinergic
What is the agonist/ligand and antagonist associated with vesicular ACh transporter?
- agonist: ACh in cytoplasm
- antagonist: vesamicol
What is the agonist/ligand and antagonist associated with choline transporter?
- agonist: choline in the synapse
- antagonist: hemicholinium-3 (HC-3)
What is the agonist/ligand and antagonist associated with ACh esterase (AChE)? Which antagonists are reversible/irreversible?
- agonist: ACh in the synapse
- reversible antagonist: physostigmine, neostigmine, pyridostigmine
- irreversible antagonist: sarin, VX, organophosphates
What is the agonist/ligand and antagonist associated with nicotinic AChR? Which antagonist is reversible/irreversible?
- agonist: ACh, nicotine, succinylcholine
- reversible antagonist: D-tubocurarine
- irreversible antagonist: neonicotinoids
What is the agonist/ligand and antagonist associated with muscarinic AChR? Which drug is parasympathomimetic/parasympatholytic? Which drug is used to treat PD?
- agonist: ACh, muscarine (parsympathoMIMETIC)
- antagonist: atropine (parasympathoLYTIC), orphenadrine (PD treatment)
