Adrenergic Receptors

Question 1

What do preganglionic sympathetic fibers release?

Answer 1

ACh

Question 2

What do preganglionic parasympathetic fibers release?

Answer 2

ACh

Question 3

What is the craniosacral division of the ANS?

Answer 3

Parasympathetic

Question 4

What is the thoracolumbar division of the ANS?

Answer 4

Sympathetic

Question 5

Preganglionic Sympathetic

Answer 5

Short pre-ganglionic cells

Question 6

Postganglionic Sympathetic

Answer 6

Long-post ganglionic cells

Question 7

Preganglionic Parasympathetic

Answer 7

Long pre-ganglionic cells

Question 8

Postganglionic Parasympathetic

Answer 8

Short post-ganglionic cells

Question 9

What are exceptions to the NT release by the ganglionic fibers?

Answer 9

Post-ganglionic sympathetic fibers that innervate sweat glands and some skeletal muscle blood vessels that release ACh not NE.

Question 10

What do postganglionic sympathetic fibers release?

Answer 10

E and NE

Question 11

What do postganglionic parasympathetic fibers release?

Answer 11

ACh

Question 12

What is the function of the parasympathetic system on the eye?

Answer 12

Innervation of circular (or sphincter) muscles of pupil - constriction (miosis)

Question 13

What is the function of the parasympathetic system on the heart?

Answer 13

Innervates sinoatrial node to reduce heart rate, and AV node to slow conduction.

Question 14

What is the function of the parasympathetic system on the bronchioles?

Answer 14

Innervates smooth muscle of bronchi – causes constriction

Question 15

What is the function of the parasympathetic system on the GI tract?

Answer 15

Innervates all portions of the GI tract to promote secretions and motility

Question 16

What is the function of the parasympathetic system on the bladder?

Answer 16

Innervates detrusor muscle, when activated causes bladder emptying

Question 17

What is the function of the sympathetic system on the eye?

Answer 17

Innervates radial (or dilator) muscle causes mydriasis
Innervates ciliary body to stimulate production of aqueous humor

Question 18

What is the function of the sympathetic system on the heart?

Answer 18

Accelerated sinoatrial node pacemaker depolarization (increased heart rate).

Question 19

What is the function of the sympathetic system on the bronchiole?

Answer 19

Relaxation of smooth muscle lining the bronchioles - causes dilation

Question 20

What is the function of the sympathetic system on the blood vessels?

Answer 20

Contraction and relaxation - dependent on receptor population expressed in targeted vascular bed (e.g., alpha1 vs. beta2), as well as the ligand mediating the vascular response.

Question 21

What is the function of the sympathetic system on the GI tract?

Answer 21

Decreased motility, can override normal enteric nervous system during fight or flight

Question 22

What is the function of the sympathetic system on the bladder?

Answer 22

Inhibits emptying by contracting urethral sphincters and relaxing body of bladder

Question 23

How does sympathetic activation increase the HR?

Answer 23

Sympathetic activation increases inward calcium current and the funny current to promote faster spontaneous depolarization during phase 4 of sinoatrial node action potential and lower threshold for activation.

Sympathetic activation also stimulates greater calcium influx into myocytes during depolarization culminating in greater contractile force of the heart.

Question 24

What is the function of the sympathetic system on metabolism?

Answer 24

Increases blood sugar (gluconeogenesis, glycogenolysis, lipolysis)

Question 25

What converts DOPA to NE?

Answer 25

Dopamine beta-hydroxylase

Question 26

What is the signaling pathway of a1 adrenergic receptors?

Answer 26

Positively coupled to Phospholipase C (PLC) via

Gq/11 α protein of the heterotrimeric G protein family to increase IP3/DAG.

Question 27

What is the effect of E and NE on a1 receptors in smooth muscle?

Answer 27

Vascular smooth muscle contraction

Question 28

How do E and NE cause vascular smooth muscle contraction via a1 receptors?

Answer 28

NE, EPI or other α1 -adrenergic receptor agonists bind to α1-adrenergic receptor of vascular smooth muscle, the Gαq subunit activates PLC, which liberates inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 activates IP3 receptor that also acts as a calcium release channel in the sarcoplasmic reticulum. When activated the IP3 receptor releases stored calcium into the intracellular space, thereby increasing calcium concentrations and stimulating smooth muscle contraction.

Question 29

What is the signaling pathway of a2 adrenergic receptors?

Answer 29

Negatively couple to adenylyl cyclase via Gαi subunit which inhibits cAMP formation.

Question 30

What is the effect of a2 receptor activation?

Answer 30

Decreased NT release

Question 31

How does a2 receptor activation cause decreased NT release?

Answer 31

Pre-synaptic α2 receptor activation decreases neurotransmitter release (reduced calcium influx). Agonist ligand binds to pre-synaptic α2 adrenergic receptor and inhibits adenylyl cyclase in the pre-synaptic cell which reduces cAMP and, in turn, reduces activation of phosphokinase A (PKA). Consequently, phosphorylation of N-type calcium channels on nerve terminals is reduced, thereby reducing calcium influx during membrane depolarization and reducing vesicular release of neurotransmitter.

Question 32

What is the signaling pathway of b1 adrenergic receptors?

Answer 32

Positively couple to adenylyl cyclase via Gαs-proteins – increases cAMP

Question 33

What is the effect of b1 receptor activation on the heart?

Answer 33

Increased HR and contractility

Question 34

How does b1 activation increase HR?

Answer 34

Activation of adenylyl cyclase and increase of cAMP can activate PKA to promote phosphorylation of calcium channels in the membrane of sinoatrial node cells leading to increased inward calcium current and thus faster nodal cell depolarization to the firing threshold.

Question 35

How does b1 activation increase contractility?

Answer 35

Increased cAMP leads to increased PKA-dependent phosphorylation of L-type calcium channels in myocyte membrane which leads to enhanced calcium influx and larger trigger signal for release of calcium from the sarcoplasmic reticulum into the intracellular space. Trigger calcium also enters the sarcoplasmic reticulum increasing calcium storage such that next trigger initiates larger efflux of calcium through ryanodine receptors.

Question 36

What is the signaling pathway of b2 adrenergic receptors?

Answer 36

Positively couple to adenylyl cyclase via Gαs protein - increases cAMP

Question 37

What is the effect of b2 activation on vascular smooth muscle?

Answer 37

Vascular smooth muscle relaxation

Question 38

How does b2 activation cause the relaxation of vascular smooth muscle?

Answer 38

cAMP activates PKA which phosphorylates and inactivates myosin light chain kinase (MLCK). Normally MLCK phosphorylates the light chain of myosin enabling actin and myosin cross-bridge formation and smooth muscle contraction. Phosphorylation of the MLCK enzyme by PKA reduces the affinity of MLCK for Ca-calmodulin resulting in reduced activity of the enzyme so its ability to phosphorylate myosin light chain is inhibited. In this case PKA inactivates MLCK. Therefore, β2 adrenergic receptor activation leads to reduced smooth muscle contraction. β2 adrenergic receptors are highly expressed on smooth muscle of the bronchi and some vascular beds and therefore regulates the degree of airway constriction as well as peripheral vascular resistance.

Question 39

How does a2 receptor activation lead to vasoconstriction?

Answer 39

The Gαi subunit, to which the α2 adrenergic receptor is coupled, inhibits adenylyl cyclase, which, in turn, inhibits cAMP and PKA. PKA normally phosphorylates and inhibits the activity of myosin light chain kinase. Therefore, inhibition of PKA leads to activation of MLCK and vascular smooth muscle constriction.