Exam 2 Flashcards
Steps of drug facilitation
- Drug acts as NT precursor
- Drug stimulates NT release
- Drug stimulates postsynaptic receptors
- Drug blocks autoreceptors; increase release of NTs
- Drug inhibits NT degredation
- Drug blocks reuptake
Steps of drug inhibition
- Drug inhibits NT synthesis
- Drug inhibits storage of NTs in vesicles
- Drug inhibits release of NT
- Drug blocks postsynaptic receptors
- Drug stimulates autoreceptors; inhibits release of NTs
how is acetylcholine made
in axon terminals, acetyl coenzyme A (acetyl CoA) + choline
what is the catalyst of ACh synthesis
choline acetyltransferase (ChAT)
what breaks down ACh and where
acetylcholinesterase (AChE) in the synapse
ACh in PNS
involved in signaling in sympathetic and parasympathetic (ANS) and neuromuscular junction (SNS)
ACh is primary NT in PNS
ACh in CNS
cholinergic neurons clustered in a few areas
striatum + basal forebrain cholinergic system (BFCS)
basal forebrain cholinergic system
related to cognition and learning (muscarinic antagonists disrupts learning)
in nucleus basalis, substantia innominata, medial septal nucleus (projects throughout forebrain, limbic system, and hippocampus)
striatum
related to Parkinson’s disease (anticholinergics decrease Parkinson’s symptoms)
stimulated by DA neurons in nigrostriatal pathway
why are the effects of ACh on peripheral tissues important?
ACh is important in many tissues of the body (everywhere), so it has many side effects when used for treatment
Black widow toxin on ACh
activates ACh synapses by massively increasing ACh release in PNS
vesicular acetylcholine transporters (VAChT)
vesicles in axon terminal loaded with ACh by VAChT
can be blocked by vesamicol
Botulinum toxin on ACh
inhibits ACh synapses by interfering with SNARE proteins at presynaptic terminal to prevent vesicular release
what is ACh broken down into?
AChE breaks down ACh into choline and acetic acid
drugs that block AChE
physostigmine (eserine) — pyridostigmine (mesinon) and neostigmine (prostigmin)
sarin (pyridostigmine bromide (PB - reversible AChE inhibitor; prevents nerve gas poisoning)
criteria for identifying neurotransmitters
- chemical must be synthesized or present in neuron
- when released, chemical must produce a response in target cell
- same receptor action must occur when chemical is experimentally or artificially placed on target
- there must be a mechanism for removal
Alzheimer’s Disease and ACh
massive neuronal loss in cortex and hippocampus (+ BFCS projecting to these parts)
AChE inhibitor drugs show little improvement to increase ACh levels
nicotinic AChR
ionotropic receptor (ligand gated ion channel)
heteropentamer or homopentamer (5 subunits or alpha-7)
ligands include acetylcholine and nicotine
what happens when a ligands binds to nicotinic AChR?
a channel permeable to Na+ is gated
some subtypes permeable to Ca(2+)
two molecules of ACh must bind to alpha subunits at the same time to open channel for Na+
agonist and antagonist of nicotinic AChR
agonist = nicotine
antagonist = D-tubocurarine
why are larger doses of nicotine and ACh needed to activate for muscles?
nicotinic receptors on muscles are less sensitive
