Peripheral Nervous System Pharmacology: Introduction

Question 1

Review the process of AP release of neutrotransmitters

Answer 1

excitatory pulses once reaching threshold send and AP down the axon via voltage gated ion channels
voltage gated Ca channels cause the fusion of vesicles to the synapse, allowing release of neurotransmitters

(neurotransmitters are bound to ligand-gated ion channels which trigger G-protein coupled receptors or are taken up by uptake transporters)

Question 2

Describe the axon branching pattern and ganglia arrangement of parasympathetic autonomic division.

Answer 2

preganglionic neurons arise from the CNS and exit the spinal cord through cranial and sacral spinal nerves, axons synapse in peripheral ganglia that are close to or within the target organ (discrete output)

Question 3

Describe the axon branching pattern and ganglia arrangement of sympathic autonomic division.

Answer 3

preganglionic neurons arise in CNS and send axons through the thoracic and lumbar spinal nerves, axons synapse in 3 pre vertebral ganglia or 22 pairs of paravertebral ganglia, postganglionic neurons arise within ganglia, sending axons out to synapse at end organs (distributed output)

Question 4

Blood vessels are innervated by ____ but not ____ but instead have receptors for parasympathetic neurotransmitters acting in local effects.

Answer 4

sympathetic but not parasympathetic

Question 5

List 4 organs with single (sympathetic) innervation.

Answer 5

blood vessels
spleen
piloerector muscles
sweat glands

Question 6

2. What neurotransmitters do cholinergic and adrenergic neurons release?

Answer 6

Choinergic (acetylcholine)

Adrenergic (norepinephrine, epinephrine or dopamine)

Question 7

Name the types of neurons that release ACh

Answer 7

All motor neurons to skeletal muscle,
all preganglionic ANS neurons,
all postganglionic parasympathetic neurons
and some postganglionic sympathetic neurons

Question 8

Name the types of neurons that release adrenergic transmitters.

Answer 8

most postganglionic sympathetic neurons (NE)
adrenal medulla (E and NE)
some post ganglionic neurons (DA)

Question 9

Describe the process by which a sympathetic cholinergic neuron arises form functional noradrenergic neurons (2 types).

Answer 9

target dependent switches: the target tissue secretes factors that induce a cholinergic phenotype
target independent: ganglion cells in the sympathetic chain express cholinergic phenotype with NE traits prior to innervation of target organs

Question 10

What is the parasympathetic postganglionic cell type and receptor type?

Answer 10

cholinergic with muscarinic receptor

Question 11

What is the 3 possibilities for post ganglionic sympathetic cell type and receptor type

Answer 11

sweat glands: cholinergic with muscarinic receptor
cardiac and smooth muscle: adrenergic with a/B receptors
renal vascular SM: adrenergic with dopamanergic receptors

Question 12

2. What enzyme carries out the biosynthesis and metabolism of acetylcholine?

Answer 12

choline-acetyl transferase

degraded in hydrolysis by acetylcholine esterase

Question 13

Name the two transporters responsible for Ach re-uptake into vesicles as well as the proteins required for fusion of the vesicle to the synapse.

Answer 13

CHT is an Na dependent transporter of choline reuptake
VAT is a proton driven transporter of Ach into the vesicles (gradient established by Na/H ATPase)

VAMP and SNAPs are required for fusion to the synapse (site of action for botox)

Question 14

List the enzymes that are required in the synthesis of NE and Epi.

Answer 14

tyrosine > DOPA = tyrosine hydroxyls
DOPA> dopamine= aromatic amino acid decarboxylase
dopamine> NE= dopamine B hydroxyls
NE> Epi = Phenylehtanolamine-N-methyltransferase

Question 15

What enzyme are used in the metabolism of dopamine?

Answer 15

(MAO, ALDH) > DOPAC> (COMT) > homovanillic acid OR
(COMT) > 3-Methoxytyramine > (MAO, ALDH)> HVA

**HVA is used as a marker in urine for DA metabolism

Question 16

What are possible metabolism pathways for NE and Epi?

Answer 16

each can be metabolized by COMT and MAO/ALDH in either order to give 3 different metabolites that eventually converge on vanillylmandelic acid (VMA)

Question 17

What are the actions of the tyrosine/Na+ dependent transporter, NET and VMAT?

Answer 17

tyrosine is taken back into the cell via tyrosine/Na+ dependent transporter or NET (important site of drug action), where it is converted to dopa in the cytoplasm by tyrosine hydroxylase and then VMAT (which can transport DA, NE and serotonin) moves dopamine into the vesicle where it can be converted into NE

Question 18

Describe the 2 types of cholinergic receptors that respond to ACh.

Answer 18

1. Muscarinic receptors: g protein coupled, M1-M5

2. Nicotinic receptors: ligand gated ion channels, Nm and Nn

Question 19

Describe the 3 types of adrenergic receptors that to catechoamines.

Answer 19

all are G protein coupled

1. Two types respond to NE and Epi: a receptors (a1 and a2 which are divided into 3 subtypes) and B receptors (B1-B3)
2. One type of receptor responds to DA: D1-D5

Question 20

What types of neurons act on the iris circular muscle and which act on the iris radial muscle?

Answer 20

circular muscle: M3 activation causes muscle contraction (para)
B2 activation causes muscle relaxation (slight)(symp)

radial muscle: only a1, activation causes muscle contraction (simp)

Question 21

What types of neurons act to shape the lens or in eye secretion?

Answer 21

cilliary smooth muscle: M3 activation muscle contraction (allows for accommodation) (parasym)
B2 activation causes muscle relaxation (symp)

lacrimal glands: M3 activation causes lacrimation (sympathetic)

Question 22

What types of neurons act on bronchial smooth muscle?

Answer 22

M3 activation causes muscle contraction (para)

B2 activation cause muscle relaxation (symp)

Question 23

What types of neurons act on bronchial glands?

Answer 23

M3 activation causes viscous mucous secretion (symp)

B2 activation causes watery secretion via CFTR (para)

Question 24

What types of neurons act on the heart?

Answer 24

M2 activation: bradycardia, decreed AV conduc. and decreased atrial contractility
B1 and B2 activation causes tacky, increased AV, His-Purkinje and ventricular automaticity and conductivity

Question 25

What types of neurons act on the vascular system?

Answer 25

``` M3 activation of endothelial cells leads to NO release a1 and a2 activation of SM causes constriction B2 activation (liver and skeletal muscle MLCK inhib) cases relaxation D1 activation: dilation of renal arteries and arterioles ```

Question 26

What are neuron vericosities?

Answer 26

found along the length of the axon can result in distributed activation (ie. muscarinic neurotransmission in the heart)

Question 27

Describe the mechanism of action of B1 receptors on the heart.

Answer 27

B1 is a Gi coupled receptor that increases cAMP, activates PKA and PKA phosphorylates Ca++ channel to allow influx (reach threshold on pacemaker cells or plateau) and increase HR, conduction velocity and force of contraction

Question 28

Which neurotransmitter(s) readily bind B2?

Answer 28

NE doesn't "see" B2 very well, but Epi does, during flight or fight B2 are activated by Epi

Question 29

What types of neurons act in the intestine?

Answer 29

M3 activation causes contraction of intestinal walls (peristalsis) (para) a1 and B2 activation cause relaxation caused by hyperpolarization via Ca++ dependent K+ channels gastrointestinal secretions M3 activation increases secretion B2 activation decreases secretion, except amylase

Question 30

What types of neurons act on gastrointestinal sphincters?

Answer 30

``` M3 activation (relaxation) a1 activation (contraction) ```