med chem cholinergic neurotransmission 2
Terms
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- sympathetic division outflow
- thoracolumbar region of spinal cord
- sympathetic division pregang neuron length
- short
- sympathetic division postgang neuron length
- long
- sympathetic division innervation of adrenal gland
- direct innervation (passes through the ganglia but there is no synapse)
- parasympathetic division outflow
- cranio-sacral region of the spinal cord
- parasympathetic division pregang neuron length
- long
- parasympathetic division postgang neuron length
- short
- parasympathetic neurons do not innervate (4)
-
adrenal medulla
kidney
pilomotor muscle
sweat gland - definition of neurotransmitter
- endogenous chemical entities that facilitate the transmission of electrical (nerve) impulses
- in general, NTs are synthesized, stored, released, and inactivated ________ but effects are ____ ________
-
locally
far reaching - examples of NTs
-
acetylcholine
monoamines
amino acids
peptides - monoamine NTs
-
epinephrine
norepinephrine
serotonine - amino acid NTs
-
glycine
GABA - GABA stands for
- gamma amino butyric acid
- peptide NTs
-
substance P
enkephaline
endorphins - ionotropic effect
-
when a receptor is also an ion channel
immediate effect - metabotropic effect
-
when a receptor produces a 2nd messenger
lag time - cholinergic neurons
- neurons that release acetylcholine
- ACh is the neurotransmitter of
-
all pregang fibers of symp & para
all postgang of para
adrenal medulla
somatic NS
few postgang of symp (sweat & salivary glands)
some CNS neurons - role of ACh in CNS (4)
-
cognition
memory
behaviour
coordination of movement - role of ACh in eyes
- constiction of pupils (miosis) ~ near vision
- role of ACh in lungs & bronchioles
-
incr constriction of bronchioles
incr secretion from the tracheobronchial mucosa - role of ACh in GIT
-
incr contraction & scretions of stomach (incr digestion)
incr motility of intestine (parastaltic waves) - role of ACh in bladder
-
contraction ~ micturition
contraction of detrussor muscle, relaxation of sphincter & trigone muscles - role of ACh in exocrine glands
- incr secretions of salivary, sweat, & lacrymal glands
- role of ACh in heart
-
decr rate of contraction (- chronotropic)
decr force of contraction (- ionotropic) - role of ACh in blood vessels
- relaxation of smooth muscles of blood vessels - vasodilation
- what kind of receptor does acetylcholine bind to?
- cholinergic receptors
- what are the 2 types of cholinergic receptors
-
nicotinic
muscarinic - where is nicotine found?
- tobacco
- where is muscarine found?
- poisonous mushroom ~ amanita muscarina
- what 2 rings does nicotine have in its structure?
-
pyridine
pyrrolidine - what are nicotine receptors coupled to?
- ion channels
- a nicotinic receptor has how many subunits? where does ACh bind?
-
5 subunits - 2 alpha, 1 beta, 1 gamma, 1 delta
ACh binds to alpha subunit - where are 3 places that nicotinic receptors are located
-
neuromuscular junction
autonomic ganglia
CNS - what is myasthenia gravis?
-
an autoimmune disease
-muscle weakness, drooping eyelids
-lethargy
-possible paralysis
nicotinic receptors at NMJ destroyed by antibodies - what do muscle relaxants target
- nictonic receptors at NMJ
- a blockade of the autonomic ganglia can cause:
- sever hypotension
- what are the 2 nicotinic receptor subtypes
- N1 & N2 receptors
- N1 nicotinic receptors (location, blocked by?)
-
located at NMJ
blocked by: decamethonium, d-tubocurarine, succinylcholine - N2 nicotinic receptors (location, blocked by?)
-
located at autonomic ganglia
blocked by: hexamethonium - which receptor mediates most of ACh responses
- muscarinic
- action of ACh on muscarinic receptors (6)
-
stimulates secretions of salivary & sweat glands
stimulates secretions & contraction of gut
constricts airways of respiratory tract
decreases contraction of heart
relaxes smooth muscles of blood vessels - where are muscarinic receptors located
- in CNS & PNS
- structure of muscarinic receptors
-
7 transmembrane helical protein domains
-extracellular domains
-intracelluar domains - g-protein coupled receptors
-
muscarinic receptors
g-protein: family of proteins
bind to guanine nucleotides - M1 muscarinic receptor location
-
mostly in CNS
also in GIT - M2 muscarinic receptor location
- mostly in the heart
- M3 muscarinic receptor location
- exocrine glands & smooth muscle
- M4 muscarinic receptor location
- tracheal smooth muscle
- stimulation of phospholipase C
- M1, M3, M5
- inhibition of adenylate cyclaase
- M2, M4
- stereochemistry of ACh to bind at nicotinic receptor
- anti conformation - groups farthest apart
- stereochemsitry of ACh to bind at muscarinic receptor
- gauche conformation - groups near eachother
- cholinergic agonist
- agent that mimics the action of ACh at muscarinic receptors
- cholinergic antagonist
- agent that blocks the action of ACh at muscarinic receptors
- cholinergic agonists AKA
-
parasympathomimetics
muscarinic agonists
ACh agonists - cholinergic antagonists AKA
-
parasympatholytics
anticholinergics
muscarinic antagonists
cholinergic blockers
ACh antagonists - ganglionic blocker
- agent that binds & inhibits the nicotinic-receptor mediated response of ACh at the autonomic ganglia
- skeletal muscle relaxants
- agents that bind & inhibit the nicotinic-receptor mediated response of ACh at the NMJ
- what form of ACh is active
- stored ACh (when not stored, enzymes will break down)
- sources of ACh
-
most made from recycled choline
some made from serine - ACh is stored in vessels until:
- an action potential is received
- what causes the storage vesicle to fuse to the presynaptic membrane?
- Ca that diffuses inward after the action potential makes the membrane more permeable
- ACh is inactivated by:
-
AChE (acteylcholine esterase)
BuChE (butyrylcholine esterase) - what are the 2 ways for the reuptake of choline
-
high affinity reuptake
low affinity reuptake - high affinity reuptake
-
major mode
energy dependent
blocked by hemicholinium - low affinity reuptake
-
not considered important
not energy dependent
likely occurs by diffusion - AChE
-
major mode of inactivation
found in and around neurons
specific for ACh & propionylcholine - BuChE
-
minor mode of inactivation
found in plasma
broad substrate range