Autonomic Pharmacology Principles

Question 1

On what basis is the ANS divided? Why is this important?

Answer 1

the division is entirely anatomical, which means that the two do overlap with regards to neurochemistry at times

Question 2

What are the various divisions of the ANS?

Answer 2

• the sympathetic nervous system, including the adrenal medulla
• the parasympathetic nervous system
• the enteric nervous system

Question 3

Describe the basic anatomy of the sympathetic nervous system.

Answer 3

• it has thoracolumbar outputs
• shorter preganglionic fibers terminate in ganglia called the paravertebral chains)
• longer postganglionic fibers innervate peripheral tissues
• furthermore, it is important to remember that the sympathetic system, unlike the parasympathetic, is diffuse, meaning that one preganglionic fiber may innervate several postganglionic fibers

Question 4

How does the adrenal medulla connect to the autonomic nervous system?

Answer 4

• it can be equated to a postganglionic sympathetic neuron

- it receives sympathetic preganglionic fibers and releases epinephrine and norepinephrine into the blood

Question 5

Describe the basic anatomy of the parasympathetic nervous system.

Answer 5

• it has craniosacral outputs
• long preganglionic fibers terminate in parasympathetic ganglia
• short postganglionic fibers originate in those ganglia and innervate organs
• these connections tend to be more discrete than those of the sympathetic system, meaning that, for the most part, there is a 1:1 connection between pre and postganglionic fibers

Question 6

Describe the basic anatomy of the enteric nervous system.

Answer 6

• it innervates the walls of the GI system, forming the myenteric plexus and the sub mucous plexus (aka plexus of Meissner)
• it receives parasympathetic preganglionic fibers and sympathetic postganglionic fibers

Question 7

Which division of the autonomic nervous system has diffuse connections? What does this mean?

Answer 7

a single sympathetic preganglionic fiber may innervate numerous postganglionic fibers, there isn’t a 1:1 relationship as there is in the more “discrete” PNS

Question 8

What NT system mediates the synapse between pre- and postganglionic sympathetic fibers? What about those the parasympathetic system?

Answer 8

both the SNS and PNS utilize ACh and nicotinic receptors at the preganglionic-postganglionic synapse

Question 9

Postganglionic sympathetic neurons utilize what NT system?

Answer 9

most utilize adrenergic receptors, however, a few utilize acetylcholine and some, mostly in the CNS, utilize DA

Question 10

Postganglionic parasympathetic neurons utilize what NT system?

Answer 10

most utilize acetylcholine, however, a few utilize nitric oxide or peptide neurotransmitters

Question 11

What NT mediates the NMJ?

Answer 11

acetylcholine

Question 12

Most autonomic nerves release a co-transmitter in addition to ACh or NE. What are these co-transmitters? Why are they released?

Answer 12

• vasointestinal peptide alongside ACh
• neuropeptide Y with NE
• they provide long lasting, slowly developing activation of the postsynaptic target tissue

Question 13

Describe acetylcholine synthesis, release, and catabolism.

Answer 13

• acetyl-Co is synthesized in the mitochondria and choline is transported into the neuron from the synaptic cleft (recycled)
• choline acetyltransferase (ChAT) synthesizes acetylcholine
• ACh is then transported into a synaptic vesicle via vesicular acetyl transporter (VAT)
• an action potential triggers a calcium influx, which induces vesicular fusion and NT release
• in the synaptic cleft, ACh is catabolized by AChE into choline and acetate
• the choline is recycled by the presynaptic cell

Question 14

What is butyrylcholinesterase?

Answer 14

a non-neuronal AChE expressed by RBCs that essentially eliminate all ACh that reaches the blood stream

Question 15

Describe adrenergic synthesis, release, and catabolism.

Answer 15

• tyrosine hydroxylase converts tyrosine to dopa in the rate-limiting step
• dopa is then converted to dopamine by dopa decarboxylase
• dopamine is packaged into a synaptic vesicle by VMAT where it is converted to NE by dopamine-B-hydroxylase
• an action potential triggers a calcium influx, which induces vesicular fusion and NT release
• it is primarily cleared form the synaptic cleft via uptake 1, which transports it back into the presynaptic terminal, and uptake 2, which transports it into the postsynaptic terminal,
• MAO and COMT are responsible for turnover and catabolism, generating the end product VMA (3-methoxy-4-hydroxymandelic acid), which undergoes renal excretion

Question 16

What is VMA (aka 3-methoxy-4-hydroxymandelic acid) and how is it clinically useful?

Answer 16

it is the end product of NE catabolism by MAO and COMT, which is excreted in the urine and can be used as a measure of sympathetic activity

Question 17

What class of receptor is the muscarinic acetylcholine receptor?

Answer 17

it is a GPCR

Question 18

What class of receptor is the nicotinic acetylcholine receptor?

Answer 18

it is an ion channel

Question 19

What class of receptor are the adrenergic receptors?

Answer 19

they are all GPCRs

Question 20

What are nonadrenergic, noncholinergic neurons? Where are they important?

Answer 20

• neurons in the ANS that are neither cholinergic nor adrenergic
• instead they primarily use NO, peptides, and purines
• they are particularly important in the GI and GU systems

Question 21

Generally speaking, what are the functions of the parasympathetic and sympathetic nervous systems?

Answer 21

• the PNS produces energy conservation (slowing of heart rate, stimulation of digestive activity)
• the SNS is recruited at times of stress (cardiac stimulation, increased blood glucose, cutaneous vasoconstriction)

Question 22

Is the parasympathetic or sympathetic system responsible for most of the underlying tone at most organs? Where is this not true?

Answer 22

• the PNS is responsible for the underlying tone of most organs
• the primary exception is peripheral vasculature, which has only sympathetic tone and does not receive any innervation by the PNS

Question 23

Describe the ANS innervation of endothelial cells.

Answer 23

• the entirety of their underlying tone is sympathetic because they receive no parasympathetic innervation
• however, they do express muscarinic cholinergic receptors, which can be activated pharmacologically but don’t experience endogenous activation, resulting in NO release and vasodilation

Question 24

What is the function of muscarinic cholinergic receptors found on endothelial cells?

Answer 24

while they have no endogenous activation, they can be activated pharmacologically, which causes the release of NO and subsequent vasodilation

Question 25

Describe autonomic control of cardiovascular function, particularly their mechanism and effect on MAP.

Answer 25

• the sympathetic system has the biggest impact on MAP by increasing peripheral vascular resistance
• the parasympathetic system functions to reduce MAP by reducing the heart rate, which lowers the cardiac output
• the sympathetic system, however, can also increase contractile force and thus stroke volume, while also increase venous tone and thus increasing venous return

Question 26

Describe autonomic control of the eye. What receptor is expressed by each important structure?

Answer 26

• the radial muscle has alpha-adrenergic receptors and increases the diameter of the pupil
• the secretory epithelium of the ciliary body has beta-adrenergic receptors and is stimulated to form more aqueous humor
• the sphincter muscle has muscarinic receptors and reduces the diameter of the pupil
• the ciliary muscle has muscarinic receptors and contracts, rounding the pupil for near vision and enhancing the outflow of aqueous humor via the canal of Schlemm

Question 27

How can you use the autonomic innervation of the eye to treat glaucoma?

Answer 27

• an beta-adrenergic receptor inhibitor will reduce secretion of aqueous humor
• a muscarinic agonist will increase the outflow of aqueous humor via the canal of Schlemm

Question 28

What are alpha2 receptors?

Answer 28

presynaptic receptors on postganglionic sympathetic neurons that tend to inhibit the release of NE

Question 29

Presynaptic auto receptors tend to have what function?

Answer 29

they tend to inhibit vesicular release