phramacology cholinergic transmission
Terms
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- acethlcholine synthesis happens where?
- in the cholinergic nerve terminal cytoplasm
- Ach synthesized by the action of?
- enzyme Choline Acetyltransferase (ChAT) on the precursors choline (Ch) and acetylcoenzyme A (acetyl-CoA)
- choline is provided mainly through?
- high-affinity sodium co-transport pumps (which require energy) located on the nerve terminal membrane
- De Novo synthesis of Ch
-
occur to a limited extent
from choline-containing phospholipids
acts to provide enough Ch to make up for amt. lost in the synapse - Acetyl-CoA is synthesized from?
- pyruvate & acetate, acetylating coenzyme A in mitochondoria
- Hemicholinium-3 (HC-3) inhibits?
-
inhibit high affinity uptake carriers of Ch
leads to eventual depletion of Ach in the nerve terminal - Vesamicol inhibits?
- inhibits Ach transport system on the vesicles
- Botulinium Toxin (Bo Tox)
-
binds to sites on the nerve terminal
causes irreversible inhibition of the release of Ach from the nerve terminal - Bo Tox blocks?
- blocks the ability of Ach vesicles to fuse with the internal nerve terminal cell wall and excytosis
- black widow spider venom
- triggers the exocytosis of Ach-containing vesicles
- acetylcholinesterase catabolizes Ach to?
- Ch and acetic acid
- 2 cholinergic receptors
- muscarinic and nicotinic
- muscarinic receptors
- comprised of a family of receptors (M1-M5)
- M1 location?
- in autonomic ganglia and CNS
- M2 location?
- on supraventricular regions of heart
- M3 location?
-
on smooth muscles
glands
vascular endothelial cells - M1 & M3 are coupled to?
- phospholipase C via G proteins
- phosphatidylinositol polyphosphates(PIP)spilits into?
-
inositol 1,4,5 triphosphate (IP3) &
Diacylglycerol (DAG)
by activation of M1 & M3 receptors - IP3
-
water soluble (in cytoplasm)
act on IP3 receptors on the sarcoplasmic reticulum &
increase Ca release - DAG
-
lipid soluble (in cell memb)
along with increase Ca,
activates protein kinase C (PKC) - muscarinic Ach receptors
- belong to a class of metabotropic receptors which use G proteins as their signalling mechanism
- nicotinic receptors
- ganglionic receptors in both symp/para-symp and neuromuscular junctions
- Muscarinic receptors are found in?
- parasympathetic nervous system
- M1
-
late EPSP in ganglia
blocked by Atoropine
selectively stimulated by Oxotremorine - EPSP
- excitatory post-synaptic potential
- Pirenzepine
- fairly selective M1 antagonist
- M2
-
mainly cardiac (decreases AV nodal conduction & SA automaticity, < HR)
blocked by Atropine - AF-DX116
- selective M2 antagonist
- M3
-
exsalivation
urination
defecation
pupillary constriction
bronchoconstriction - Hexahydrosilafenidol
- selective M3 antagonist
- M4
-
mainly in CNS
antagonized by Himbacine - M5
- exact importance and locations still unclear
- ganglionic nicotinic receptors stimulated by?
- Ach & Dimethylphenyl-piperazinium (DMPP)
- ganglionic nicotinic receptors antagonized by?
- Trimethaphan (Arfonad)
- neuromuscular nicotinic receptors stimulated by?
- nicotine and Ach
- Phenyltrimetyl ammonium (PTMA)
- a selective agonist of neuromuscular nicotinic receptor
- D-tubocurarine (Tubarine)
- a non-depolarizing antagonist of neuromuscular nicotinic receptor
- alpha-bungarotoxin
-
from snake venom
almost irreversible antagonist of neuromuscular nicotinic receptor - neuromuscular depolarizing blockers
-
Decamethonium
Succ (Anectine)
initially stimulate receptor, then block - autoreceptors
-
mainly muscarinic (M1, M2, ??)
inhibit further release of Ach
nicotinic autoreceptors found, but they tend to increase rather than inhibit Ach release - heteroreceptors
-
innervention on nerve terminal by another type of receptor
allows control of release by another system
receptors react to circulating neurotransmitter - cycloplegia
- paralysis of accomodation from para-symp drug
- contraction of ciliary muscle
-
release the tension of suspensaory ligament
lens get thicker - relaxation of ciliary muscle
-
pulls ligament
makes lens thinner