Adrenergic Receptors Flashcards

1
Q

What do preganglionic sympathetic fibers release?

A

ACh

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2
Q

What do preganglionic parasympathetic fibers release?

A

ACh

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3
Q

What is the craniosacral division of the ANS?

A

Parasympathetic

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4
Q

What is the thoracolumbar division of the ANS?

A

Sympathetic

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5
Q

Preganglionic Sympathetic

A

Short pre-ganglionic cells

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6
Q

Postganglionic Sympathetic

A

Long-post ganglionic cells

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7
Q

Preganglionic Parasympathetic

A

Long pre-ganglionic cells

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8
Q

Postganglionic Parasympathetic

A

Short post-ganglionic cells

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9
Q

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

A

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

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10
Q

What do postganglionic sympathetic fibers release?

A

E and NE

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11
Q

What do postganglionic parasympathetic fibers release?

A

ACh

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12
Q

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

A

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

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13
Q

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

A

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

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14
Q

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

A

Innervates smooth muscle of bronchi – causes constriction

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15
Q

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

A

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

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16
Q

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

A

Innervates detrusor muscle, when activated causes bladder emptying

17
Q

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

A
Innervates radial (or dilator) muscle causes mydriasis
Innervates ciliary body to stimulate production of aqueous humor
18
Q

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

A

Accelerated sinoatrial node pacemaker depolarization (increased heart rate).

19
Q

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

A

Relaxation of smooth muscle lining the bronchioles - causes dilation

20
Q

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

A

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.

21
Q

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

A

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

22
Q

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

A

Inhibits emptying by contracting urethral sphincters and relaxing body of bladder

23
Q

How does sympathetic activation increase the HR?

A

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.

24
Q

What is the function of the sympathetic system on metabolism?

A

Increases blood sugar (gluconeogenesis, glycogenolysis, lipolysis)

25
Q

What converts DOPA to NE?

A

Dopamine beta-hydroxylase

26
Q

What is the signaling pathway of a1 adrenergic receptors?

A

Positively coupled to Phospholipase C (PLC) via

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

27
Q

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

A

Vascular smooth muscle contraction

28
Q

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

A

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.

29
Q

What is the signaling pathway of a2 adrenergic receptors?

A

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

30
Q

What is the effect of a2 receptor activation?

A

Decreased NT release

31
Q

How does a2 receptor activation cause decreased NT release?

A

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.

32
Q

What is the signaling pathway of b1 adrenergic receptors?

A

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

33
Q

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

A

Increased HR and contractility

34
Q

How does b1 activation increase HR?

A

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.

35
Q

How does b1 activation increase contractility?

A

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.

36
Q

What is the signaling pathway of b2 adrenergic receptors?

A

Positively couple to adenylyl cyclase via Gαs protein - increases cAMP

37
Q

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

A

Vascular smooth muscle relaxation

38
Q

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

A

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.

39
Q

How does a2 receptor activation lead to vasoconstriction?

A

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.