Sympathetic Nervous System and Adrenergic Receptors

Question 1

What are the neurotransmitters involved in adrenergic transmission?

Answer 1

Norepinephrine (NE), epinephrine, Dopamine (DA)

Question 2

What is the Function of NE?

Answer 2

It is the principle neurotransmitter of most postganglionic sympathetic fibers

Question 3

What is the function of epinephrine?

Answer 3

It is the major hormone of the adrenal medulla – IT IS NOT RELEASED BY NERVE ENDINGS

Question 4

What is the function of DA?

Answer 4

It is the primary neurotransmitter in the extrapyramidal system

Question 5

What is the rate-limiting step in catecholamine synthesis?

Answer 5

Tyrosine hydroxylase

Question 6

What enzyme is involved in the synthesis of epinephrine from norepinephrine?

Answer 6

PNMT

Question 7

What happened to NE when it is removed from the synaptic cleft/neuro effector junction?

Answer 7

1) Repuptake of NE via Na+ dependent norepinephrine transporter (NET) and either stored or destroyed via MAO
2) Diffusion out of synapse into the circulation and destroyed in the liver via COMT and MAO
3) Transport into effector cells followed by enzymatic deactivation

Question 8

What are the basic functions of the sympathetic nervous system?

Answer 8

1) It is an important regulator of all organ systems
2) It prepares the body for stress, muscular activities and emergencies
3) It is contrasted by the parasympathetic nervous system

Question 9

How are adrenergic receptors classified?

Answer 9

a-adrenergic:

a₁-adrenergic (post-synaptic excitatory)

a₂-adrenergic (pre-synaptic inhibatory)

b-adrenergic:

b₁-adrenergic (myocardium)

b₂-adrenergic (smooth muscle and most other sites)

b₃-adrenergic (adipocytes)

Question 10

What is the classical characterization of adrenergic receptors based on rank/order of selectivity/potency of agonists for specific receptors?

Answer 10

b-adrenergic:

isoproterenol > epinephrine ≥ norepinephrine

a-adrenergic:

epinephrine > norepinephrine >> isoproterenol

Question 11

What kind of receptors are adrenergic receptors?

Answer 11

GPCR – adrenergic responses result from g protein-mediated effects on the generation of secondary messagers and on the activity of ion channels

Question 12

What happens when a₁ receptors are activated?

Answer 12

• G_q –> PLC –> Formation of IP₃ and DAG
• IP₃ –> increases intracellular Ca⁺⁺
• Ca⁺⁺ activates PKs
• PKs phoshorylate specific substrates –> biological effect
• DAG activates PKC –> modulates signaling activity

Question 13

What happens when a₂ receptors are activated?

Answer 13

• a₂ receptors activate G_i –> inhibit adenylyl cyclase –> reduces intracellular cAMP

Question 14

What happens when b-receptors are activated?

Answer 14

• G_s stimulates adenylyl cyclase –> AC converts ATP to cAMP
• cAMP is the major secondary messanger of b-receptor activation

Question 15

Activation of b_1,2,3-receptors is mediated by which G protein?

Answer 15

G_s

Question 16

What happens when b-receptors are activated in the liver?

Answer 16

• increase in cAMP leads to activation of glycogen phosphorylase

Question 17

What happens when b-receptors are activated in heart?

Answer 17

• increase in cAMP causes increase in Ca⁺⁺ influx into the cell

Question 18

What happens when b-receptors are activated in smooth muscle?

Answer 18

• relaxation

Question 19

How are dopamine receptors classified?

Answer 19

• D₁-receptor stimulates
• D₂-receptor inhibits

Question 20

What are factors that can affect the number and function of adrenergic receptors?

Answer 20

• Catecholamines
• Drugs
• Age
• Disease states
• Receptor desensitization

Question 21

What is tachyphylaxis?

Answer 21

Rapid desensitization of receptors

Question 22

How do GPCRs mediate desensitization?

Answer 22

• Homologous: Loss of responsiveness only to receptors exposed to repeated to repeated or sustained activation
• Heterologous: Agonist desensitization of one receptor causes desensitization of another that is not activated by the agonist (e.g. secondary messenger feedback)