Sympathetic Signaling

Question 1

Where do pre-ganglionic sympathetic neurons originate and terminate?

Answer 1

Pre-ganglionic sympathetic neurons originate in the spinal cord (T1-L2) and release ACh onto nicotinic ACh receptors located in the ganglia of the paravertebral chain

Question 2

Physiologic effects - vasculature (a1)

Answer 2

Vasoconstriction (increased total peripheral resistance)

Question 3

Physiologic effects - vasculature (B2)

Answer 3

Vasodilation (decreased total peripheral resistance, increased perfusion)

Question 4

Physiologic effects - renal vasculature (D1)

Answer 4

Vasodilation

Question 5

Physiologic effects - cardiac (B1)

Answer 5

Increased heart rate (chronotropoy)
Increased AV conduction velocity
Increased contractility (inotropy)

Question 6

Postural baroreceptor reflex arc

Answer 6

Activation of the baroreceptor by increased vessel tension due to increased arterial pressure inhibits symmpathetic discharge from the medulla, resulting in vasodilation and decreased heart rate. leading to a decrease in arterial pressure

Relaxation of the baroreceptor due to decreased arterial pressure “disinhibits” sympathetic discharge, resulting in SNS-mediated release of NE at the heart (B1) causing tachycardia and blood vessels (a1) causing vasoconstriction

Question 7

Physiologic effects - Kidney (B1)

Answer 7

NE acts on B1 receptors in the kidney juxtaglomerular cells, resulting in vasoconstriction and activation of the RAAS system

Question 8

Physiologic effects - Lungs (B2)

Answer 8

Bronchodilation

Question 9

Physiologic effects - Eye

Answer 9

Pupil dilation (a1) 
Increased production of aqueous humor (B2)

Question 10

Physiologic effect - GI tract

Answer 10

Decreased motility via smooth m. relaxation (B2)

Activation of pre-synaptic A2 receptors on cholinergic neurons inhibits release of ACh, thereby inhibiting ACh-mediated muscle contraction

Question 11

Physiologic effects - genitourinary

Answer 11

Contraction of ureteral sphincter (a1) - promotes continence

Uterine smooth muscle relaxation (B2)

Question 12

Physiologic effects - skeletal muscle

Answer 12

Tremor (B2)

Question 13

Physiologic effects - metabolic

Answer 13

Liver - increased glycogenolysis causing increased blood glucose (B2)

Fat cells: Increased lipolysis (B3)

Pancreas: Decreased insulin secretion (a2)

Question 14

How is NE synthesized?

Answer 14

Neurons take up tyrosine by active transport and convert it to DOPA by tyrosine hydroxylase; DOPA is converted to dopamine and taken up into storage vesicles where it is converted to NE by dopamine-B hydroxylase

Question 15

How is NE stored and released?

Answer 15

NE is transported into storage vesicles by active transport by the VMAT pump; within the vesicles NE is protected from degradation by monoamine oxidase (MAO) located on mitochondria

Question 16

How is NE signaling terminated?

Answer 16

80% of released NE is taken back up into the presynaptic nerve terminal by the NE transporter (NET); most of this NE is taken back into storage vesicles by VMAT and a smaller percentage is metabolized by MAO

Question 17

Which receptors does NE bind?

Answer 17

A1, A2

B1

Question 18

Which receptors does adrenal epinephrine bind?

Answer 18

A1, A2

B1, B2

Question 19

What is the difference between Epi and NE?

Answer 19

Epi binds B2 receptors and NE doesn’t; therefore, Epi causes bronchodilation (i.e. in anaphylaxis) and increased perfusion of muscles

Question 20

How do A2 heteroreceptors work?

Answer 20

NE binds pre-synaptic A2 receptors on cholinergic neurons, where it inhibits release of ACh; i.e. activation of the SNS indirectly decreases GI motility via this mechanism

Question 21

Alpha 1 - Receptor Coupling

Answer 21

Gq protein-coupled; activates phospholipase C, which releases IP3 and DAG

IP3 releases intracellular stores of Ca2+ and DAG activates PKC

Question 22

Alpha 2 - Receptor Coupling

Answer 22

Gi protein coupled; inhibits adenylyl cyclase activity, decreasing cAMP levels and opening K+ channels to hyperpolarize the cell

Question 23

B1 and B2 - Receptor Coupling

Answer 23

Gs protein coupled; stimulates adenylyl cyclase, increasing cAMP synthesis; cAMP activates PKA increasing Ca2+ movement into the cell through LTCCs

Question 24

Sympatholytic action

Answer 24

Interference with adrenergic function in the presynaptic neuron; lack of specificity of action (all adrenergic synapses affected)