Exam 1 II Flashcards
What are the components of the PNS?
- afferent (somatic and visceral)
- efferent (motor)
What are the components of efferent PNS?
- somatic (skeletal muscle)
- ANS
What are components of ANS?
- symp. nervous system (thoracolumbar)
- parasymp. nervous system (craniosacral)
- enteric nervous system
Preganglionic symp. fibers
leave through the thoracic and lumbar spinal nerves
Preganglionic parasymp. fibers
- leave through cranial nerves 3,7,9 and 10
- leave sacral spinal nerves 3 and 4
location of symp. ganglia
outside the CNS in the paravertebral symp. ganglia chain
location of parasymp. ganglia
inside target organs; some in head and neck
What does every pregang. nerve release?
ACh
Describe pre and post-ganglionic neurotransmitter release of parasymp. system
- pregang. release ACh and synapse on nicotinic receptors
- postgang. release ACh and synapse on muscarinic receptors
Describe pre and post-ganglionic neurotransmitter release of symp. system
- pregang. release ACh and synapse on nicotinic receptors
- cardiac, smooth, gland cells: postgang. release NE and synapse on α and β receptors
- renal: postgang. release dopamine and synapse on D1 receptors
- sweat glands: postgang. release ACh and synapse on muscarinic receptors
- adrenal gland: release Epi, NE
Describe ganglionic neurotransmitter release of somatic system
release ACh and synapse on nicotinic receptors on muscle cells
What kind of receptor is the muscarinic receptor?
GPCR
What kind of receptor is the nicotinic receptor?
ligand activated ion channels
What are the receptors that ACh synapse on?
- muscarininc
- nicotinic
What are the receptors that NE and Epi synapse on?
α and β receptors
What is the trophotropic system?
- parasymp. system
- rest and digest -> leads to growth
What is the ergotropic system?
- symp. system
- fight or flight -> energy expenditure
Define autoreceptor
receptor that inhibits release of its own neurotransmitter; feedback inhibition
Define heteroceptor
inhibits synthesis and release of neurotransmitter that’s not its own transmitter
What are types of presynaptic neuromodulation?
- autoreceptor
- hetroceptor
What are types of postsynaptic neuromodulation?
- receptor upregulation
- receptor downregulation
Which steps in neurotransmission can we alter with drug?
- action potential
- synthesis of NT
- storage of NT
- release of NT
- termination of action of NT
- receptor binding
Describe the symp. innervation of the eye
- α1 adrenoceptor activation -> contracts radial pupillary dilator muscle to cause mydriasis
- β adrenoceptor activation -> increase secretion of aqueous humor -> intraocular pressure increases
Describe the parasymp. innervation of the eye
- happens via ACh synapse on M3 receptors
- contract circular pupillary constrictor muscle -> miosis
- contract ciliary muscle -> aq. humor flow into canal of Schlemm
- allows doe accommodation for near vision
What happens in glaucoma?
- injury blocks canal and cannot drain fluid out of eye
- increase in intraocular pressure -> damaged optic nerve
- can be genetic; canal deteriorates
What is the main cause of the predominant tone?
the parasymp. system
In which instances does the symp. system determine the predominant tone?
blood vessels and sweat glands
What is a cholinergic neuron?
a neuron that synthesizes and release ACh
What does it mean when something is innervated?
- when there is a neuron above the location that releases NT
- receptors that are not innervated will get a response from that blood flow or drugs
How is ACh synthesized?
- CHT transports choline into cell
- AcetylCoA + Choline -> ACh
Hemicholinium
blocks the action of CHT -> decreases levels of ACh
What happens after synthesis of ACh?
VAT transports it into vesicle for storage
Vesamicol
blocks activity of VAT
What effect does intracell. Ca have on nerve terminals?
fuses VAMPs and SNAPs -> exocytosis of vesicle -> release of ACh
Botulinum Toxin
inhibits fusion of VAMPs and SNAPs
What are drugs / toxins that can increase release of ACh?
- Latratoxin
- Carbachol
Toxins you should be aware of
- Latrotoxin
- Tetrodotoxin
Tetrodotoxin
inhibits action potential of cholinergic neurons
Acetylcholinesterase (AChE)
- breaks down ACh into acetate and choline
- located on post-synpt. cell
PseudoAChE
in the blood to break down any access ACh into acetate and choline
Cholinomimetics
drugs that bind on receptors that act as ACh
Anticholinergics
drugs that bind on receptors to block cholin. pathway
What are the types of cholinoceptors?
- Muscarinic receptors
- Nicotinic receptors
M2 are on which tissues?
- myocardium
- smooth muscle
- CNS neurons
M3 are on which tissues?
- exocrine glands
- vessels
- CNS neurons
Mechanism of M2
- opening of K channels
- inhibit adenylyl cyclase
Mechanism of M3
- formation of IP3 and DAG
- increased intracell. Ca
Drugs that work on muscarinic receptors do what?
favor parasymp. system
nicotinic receptors
ion channel that causes depol. of neurons and muscles
nicotinic receptors tissue distribution
- postgang. neurons
- skeletal muscle neoromuscular end plates
How many molecules of ACh needs to be bounded to nicotinic receptors?
two; after the first one binds, it is must easier for the second one to bind
Myasthenia gravis
- patient develops antibodies against their own receptors
- up to 80% of nicotinic receptors are reduced
Alzheimer’s disease
loss of cholinergic neurons in temporal lobe and entorhinal cortex brain
Where are nicotinic(m) receptors located?
skeletal muscle
Properties of ACh with respect to drug development
- non-selective
- hydrolyze quickly
- poor bioavailability
What is the effect of the acetylated choline in ACh?
quick hydrolysis
What is the effect of the quaternary amine in ACh?
poor permeability -> poor absorption
properties of muscarine
- cross BBB
- natural alkaloid found in mushrooms
- used in poison darts in which the antidote is atropine
What are the responses to mAChR agonists?
- smooth muscle contraction
- vasodilation
- increased secretion of exocrine
- miosis
- decreased heart rate
What can you alter in ACh to slow down hydrolysis?
add a carbamyl group at the ester end
effect of physostigmine
- Carbamylated AChE increases half life from 0.2ms to 15 min
- slows down hydrolysis of ACh
- reversible
effect of diethylphosphate
- half life is 8 hours
- irreversible
- phosphorylates AChE
What does MAO do?
metabolizes NE
How did the classification of alpha and beta come about?
classification based on response to NE, E, or isoproterenol
Effects of excessive ACh
- Salivation/ secretion/ sweating
- Lacrimation/ low bp
- Urination
- Defecation
- GI distress
- Emesis
Cholinergic agonists
- can cross BBB
- produce arousal and cortical activation
affects: - cognitive function
- motor control
- appetite suppression
- nociception
ACh as a choline ester
- charged molecule, cannot cross BBB
- in low doses, high affinity for M receptors
- in high doses, affinity for both M and N receptors
- 1% solution in eye to produce miosis during ophth. surgery
Bethanechol as a choline ester
- increases GI motiliy and urinary system
- tight closure of LES will prevent acid reflux
- resistant to activation by AChE
Methacholine as a choline ester
- used for diagnostic tool for asthma (back in the day; induces asthma)
- partially resistant to AChE inactivation
Carbachol as a choline ester
- resistant to AChE inactivation
- not selective
- releases ACh from nerve endings
