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105 Cards in this Set

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What are the two most general divisions of the nervous system?
Peripheral (PNS) and central (CNS)
What are the AFFERENT components of the peripheral nervous system?
The sensory receptors.
What are the two general divisions of the EFFERENT peripheral nervous system?
1. The autonomic nervous system

2. The somatic nervous system
What are the two divisions of the autonomic nervous system?
1. Symapthetic

2. Parasympathetic
What is the basic target of the sympathetic nervous system?
Smooth muscles.
What is the basic target of the parasympathetic nervous system?
Glands.
What is the basic target of the somatic nervous system?
Skeletal muscle.
What actions does the somatic nervous system control?
1. Consciously controlled functions (movement)

2. Reflexes (e.g. the withdrawl reflex)
What is the generalized action of the autonomic nervous system?
To control smooth muscle, cardiac muscle, and glands.

To deal with unconsciously controlled visceral functions (e.g. blood flow)
Somatic nervous system: neuron organization
Originates all along the spinal cord --> single neuron extends to the target --> each neuron branches and innervates many muscle fibers (a "motor unit")
Sympathetic nervous system: neuron organization
Thoracolumbar spinal cord --> short preganglionic neuron terminates in sympathetic chain --> postganglionic fibers terminate on target organ.

Note that the "crowded" environment of the sympathetic chain ganglia mean that if a neurotransmitter is released in the ganglia, it may end up affecting several different postganglionic neurons. This is responsible for the somewhat diffuse nature of the sympathetic nervous system.
Parasympathetic nervous system: neuron organization
Originates at craniosacral levels of the CNS --> Long preganglionic neuron --> short postganglionic neuron that synapses in or around target organ.
Enteric nervous system: general characteristics
Largely independant
Receives sympathetic and parasympathetic imput.
Cholenergic neurons release what?
Acetylcholine (Miochol-E®)
Adrenergic neurons release what?
Norepinephrine (Levophed ®)
Almost all efferent nerves leaving the CNS are what type of neuron (release what neurotransmitter)?
Cholenergic (ACh)
What are some examples of cholenergic neurons?
1. Somatic
2. Preganglionic sympathetics
3. Postganglionic sympathetics going to sweat glands.
4. Both pre and postganglionic parasympathetic neurons.
5. Preganglionic nerves going to the adrenal medulla.
What nerves are adrenergic?
Postganglionic sympathetics are adrenergic.
Adrenal medulla: innervation and action.
Preganglionic sympathetic neurons (cholenergic) --> innervation of catecholamine-secreting cells --> release epinephrine (80%) and norepinephrine (20%)

"The adrenal medulla is similar to a sympathetic ganglion."
Special case of sympathetic innervation of renal vascular smooth muscle?
There is some evidence that postganglionic sympathetic fibers release dopamine.
How is choline transported into a nerve terminal?

What drugs block this process?
Choline is transported into the nerve terminal via a sodium dependant transporter.

Can be blocked by hemicholinium drugs
Where is acetylCoA generated?
In glycolysis in the mitochondria.
Where is acetylcholine generated?
In the cytoplasm
What enzyme transfers an acetyl group from acetylCoA to choline?
Choline acetyl transferase (ChAT)
What is the action of choline acetyl transferase (ChAT)?
Transfers an acetyl group from acetylCoA to choline.
What loads acetylcholine into vesicles?

What drug blocks this process?
A proton antiporter loads acetylcholine into the vesicles.

Vesamicol blocks this process
What causes vesicles to be released at the neuromuscular junction?

What drug blocks this process?
Stimulus --> Na into the cell --> Ca release --> fusion of vesicles with membrane mediated by t-SNARES (syntaxin, SNAP-25) and v-SNARES (synaptobrevin, synaptotagmin)

The release of this is blocked by botulinum toxin (Botox®, Myobloc®), which cleaves synaptobrevin.
What cleaves ACh?
Acetylcholinesterase
What are the products of ACh cleavage by acetylcholinesterase?
Choline + acetate.
What is another enzyme that cleaves ACh more slowly than AChE?
Pseudocholinesterase.

(Butyrylcholinesterase, synthesized in the liver)
What is the precursor to L-DOPA?
Tyrosine
How does tyrosine get into the neuron?
Via a sodium dependant carrier
What converts tyrosine to L-DOPA?

What drug blocks this process?
Tyrosine hydroxylase.

Blocked by Metyrosine
What converts DOPA to dopamine?
DOPA decarboxylase.
What facilitates the transport of dopamine into vesicles?

What drug blocks this process?
VMAT (vesicular monoamine transporter)

Blocked by Reserpine
What converts dopamine to norepinephrine in vesicles?
Dopamine beta hydroxylase
What is a receptor on the pre-synaptic membrane that binds a product of that neuron called?
An autoreceptor
What is the main way that NE transmission is terminated?

What drugs can block this process?
1. Uptake by the PRE-synaptic neuron by a norepinephrine transporter (NET).

This process can be blocked by cocaine and tricyclic antidepressants.
What are some drugs besides NE that NET transports?
Amphetamine
Ephedrine
What are two minor ways that NE transmission is terminated?
1. Uptake by the POST-synaptic cell

2. Inactivation by MAO (monoamine oxidase) and COMT (catechol-O-methyl transferase)
(extra credit)

What is the enzyme that converts norepinephrine to epinephrine?
Phenylethanolamine-N-methyltransferase
What is the only difference between NE and E?
E has an extra methyl group.
Where is the majority of E synthesized?
In the adrenal medulla.
What two ions does the nicotinic receptor control the flow of?
Na (influx) and K (efflux)
What are the two subtypes of nicotinic receptor?

What is the clinical significance of this?
1. Receptor at the neuromuscular junction (pentamer α, β, γ, δ)

2. Receptor in autonomic ganglia (only α, β chains)

The significance of this is that different drugs can target different receptors.
What chain of the nicotinic receptor does ACh bind?
To the α chain.
(extra credit)

In adult nicotinic receptors, what chain is replaced by what?
The γ chain is replaced by the δ chain.
What are the basic characteristics of the muscarinic receptor?
It is a seven transmembrane domain monomer.
When ACh binds the muscarinic receptor, what two things get activated?
Gq, Gi
What does Gq activate?
Receptor --Gq--> PLC (phospholipase C) --> Makes PIP2 from lipids --> IP3 and DAG.

IP3 releases Ca from the SR
DAG activates PKC
What does Gi activate?
Gi opens K channels (only with M2 receptors) and inhibits adenyl cyclase.
What does PLC do?
Hydrolyzes PIP2 --> DAG + IP3
What does IP3 do?
Mediates the release of Ca from intracellular stores (e.g. ER)
What does DAG do?
Activates PKC (protein kinase C), which modulates various ion channels.
What are the main muscarinic subtypes?
M1, M2, M3
What G protein is associated with M1?
Gq
What G protein is associated with M2?
Gi
What G protein is associated with M3?
Gq
Gq activates which muscarinic subtypes?
M1, M3
Gi activates which muscarinic and adrenergic subtypes?
M2 and α2 and D2

(First-aid: MAD 2's)
What is the second messenger of the M1 receptor?
IP3, DAG
What is the second messenger of the M3 receptor?
IP3, DAG
What is the action of Gi?
Inhibits adenyl cyclase
Opens K channels in muscarinic receptors

Does NOT open K channels with adrenergic alpha-1 receptors.
In what tissues are M1 receptors located?
Autonomic ganglia
Some presynaptic sites
CNS
In what tissues are M2 receptors located?
Heart
Smooth muscle
Some presynaptic sites
In what tissues are M3 receptors located?
Most target organs
Glands
Smooth muscle
Endothelium
Prototypical muscarinic antagonist.
Atropine (Atropen®)

"Atropine blocks the muscarinic receptor"
Prototypical muscarinic agonist.
Bethanechol (Urecholine®)(Muscarine)

"Bethanechol activates muscarinic receptors"
Prototypical GANGLION nicotinic antagonist.
Trimethaphan (Arfonad®)
Prototypical GANGLION nicotinic agonist.
(DMPP) Dimethylphenylpoperazinium
Prototypical NEUROMUSCULAR nicotinic antagonist.
Tubocurarine
Prototypical NEUROMUSCULAR nicotinic agonist.
Succinylcholine (Quelicin ®, Anectine ®)

Actually is such a good "activator" of the nicotinic receptor that it opens the channels wide - eventually no signal is produced.
What is the order of sensitivity of α receptors to

Epinephrine
Norepinephrine
Isoproterenol

What about β receptors?
α = epinephrine ≥ norepinephrine ≫ isoproterenol

β = isoproterenol > epinephrine ≥ norepinephrine
What are the four basic types of adrenergic receptors?
α1, α2, β1, β2
What G-protein is associated with α1 receptors?
Gq
What G-protein is associated with α2 receptors?
Gi
What G-protein is associated with β1 receptors?
Gs --> adenyl cyclase up --> cAMP up --> PKA up.
What G-protein is associated with β2 receptors?
Gs --> adenyl cyclase up --> cAMP up --> PKA up.
What is the second messenger system involved with α1 receptors?
IP3, DAG
What is the second messenger system involved with α2 receptors?
Gi --> AC down

Note that Gi here doesn't affect K transport
What is the second messenger system involved with β1 receptors?
AC up
What is the second messenger system involved with β2 receptors?
Stimulates adenyl cyclase.
What is the predominant location of α1 receptors?

Major function?
Smooth muscles in the peripheral vasculature.

Vasoconstriction.
What is the predominant location of α2 receptors?
Presynaptic sites
Platelets
Fat cells
What is the predominant location of β2 receptors?
Smooth muscle
Cardiac muscle

Simple way to think about it: lungs and skeletal muscle.

Vasodilation, bronchodilation, HR up, contractility up, lipolysis up, glucagon release up.
β1 antagonist
Metoprolol (Toprol®, Lopressor®)
β1 agonist
Dobutamine (Dobutrex®)
α1 antagonist
Prasozin (Minipress®)
α1 agonist
Phenylephrine (Neosynephrine®)
α2 antagonist
Yohimbe (Yocon®)
α2 agonist
Clonidine (Catapres®, Dixarit®)
β2 antagonist
Butoxamine
β2 agonist
Albuterol (Ventolin®, Preventil®)
True or false: epinephrine activates all four adrenergic receptors?
True
What adrenergic receptor does E bind better than NE?
β2 receptors
β2 receptors in the bronchioles respond mainly to _______ ________.
β2 receptors in the bronchioles respond mainly to CIRCULATING EPINEPHRINE.
What is the main way by which junctional transmission is modulated?
By prejunctional receptors
Prejunctional M1 receptor: reduces or stimulates neurotransmitter release?
Stimulates
Prejunctional M2 receptor: reduces or stimulates neurotransmitter release?
Reduces
Prejunctional neuromuscular receptor: reduces or stimulates neurotransmitter release?
Stimulates
Prejunctional α2 receptor: reduces or stimulates neurotransmitter release?
Reduces
Prejunctional β2 receptor: reduces or stimulates neurotransmitter release?
Stimulates
What is a way to remember which prejunctional receptors do what?
Write it out, it alternates

M1 - stim
M2 - red
M2 - red
NM - stim
α2 - red
α2 - red
β2 - stim
β2 - stim
What is denervation supersensitivity?
A dramatic increase in the amount of receptors following denervation.

This is an example of POSTsynaptic regulation
What are two examples of POSTsynaptic signal modulation?
1. Modulation of receptor number or sensitivity (e.g. denervation sensitivity)

2. Activation of several different postsynaptic receptors (which can be excitatory (EPSP) or inhibitory (IPSP))