Adrenergic Receptors

Front 1

Where is the a-2 AR located? What action occurs when it is bound?

Back 1

*the pre-synaptic membrane
*inhibits further release of NE

Front 2

Rank the affinity of NE, epi, and isoproterenol to the alpha ARs?

Back 2

epi > NE >>> iso (no effect)

Front 3

What is the effect of binding the a-1 AR?

Back 3

Causes vasoconstriction in vascular smooth muscle.

Front 4

Rank the affinty of epi, NE, and isoproterenol on the B-1 and B-2 ARs.

Back 4

B-1: iso > epi = NE

B-2: iso > epi >>> NE (no effect)

Front 5

In what kind of tissue are B-2 ARs usually found?

Back 5

Tissue that is not inervated by sympathetic neurons.

Front 6

What effect does activation of B-1 ARs in the heart have?

Back 6

Increases HR and CTY.

Front 7

What effect does binding B-2 ARs in smooth muscle have? Those in the liver?

Back 7

*Smooth muscle: relaxtion of vascular and bronchial smooth muscle

*liver: glycogenolysis

Front 8

How many types of ARs are there?

Back 8

Nine:
3 x B subtypes
3 x a-1 subtypes
3 x a-2 subtypes

Front 9

What effect does isoproterenol have on the heart?

Back 9

Binds B-1 receptors to cause an increase in HR and CTY, and thus CO.

Front 10

What effec does NE have on bronchial smooth muscle?

Back 10

Very little - it binds poorly to B-2 ARs here.

Front 11

How is the effect of binding a B AR modulated - i.e. what are the downstream effects?

Back 11

The B ARs are G-protein linked and cause an increase in intracellular cAMP.

Front 12

How do caffeine and theophylline mimic B AR stimulation?

Back 12

They inhibit a phosphodiesterase thus increasing the intracellular cAMP.

Front 13

What is desensitization? What is the usual molecular mechanism?

Back 13

After prolonged stimulation the receptor changes to a form that does not produce the same response when stimulated. This is usually due to phosphorylation of the receptor.

Front 14

How does maintenance therapy of asthma with B-2 agonists create a danger for acute attacks?

Back 14

Prolonged stimulation results in desensitization of the B-2 receptors which are then less responsive to agents used to treat acute attacks.

Front 15

Describe how B-1 blockers used to treat HTN can precipitate a withdrawal syndrome if suddenly discontinued.

Back 15

Antagonism of the B-2 blockers results of upregulation of the receptors and of the downstream signalling molecules. When the drug is removed endogenous NE binds these "supersensitive" receptors and causes a large sympathetic innervation.

Front 16

Describe the adrenergic innervation of the heart. What are some negative effects?

Back 16

B-1 ARs are activated by iso, NE, and epi. This produces an increase in intracellular calcium which raises HR, CTY, and CO.

Angina and arrhythmias are possible.

Front 17

What effect does adrenergic stimulation have on the efficiency of the heart?

Back 17

It increases CO and greatly increases oxygen consumption, thus efficiency (CO/O2) is decreased.

Front 18

What adrenergic receptors are found in vascular smooth muscle? What are the effects of activation?

Back 18

a-1 ARs cause contraction and vasoconstriction when bound.

B-2 ARs cause relaxation and vasodilation when bound.

Front 19

What are the effects of epi and NE on the ARs in vascular smooth muscle?

Back 19

Epi binds a-1 and B-2 and thus can cause constriction or dilation depending on the tissue.

NE binds a-1 and causes constriction. It does not bind B-2 with great affinity.

Front 20

Describe the adrenergic innervation of the vessels of the skin and mucosa.

Back 20

a-1 ARs dominate, thus adrenergic innervation causes vasoconstriction.

Front 21

Describe the adrenergic innervation of the vessels of the kidneys and abdominal organs.

Back 21

a-1 ARs dominate, thus vasoconstriction occurs.

Front 22

Describe the adrenergic innervation of the vessels of the liver and skeletal muscle.

Back 22

B-2 ARs dominate, thus vasodilation occurs.

Front 23

Describe the adrenergic innervation of the capacitance veins.

Back 23

a-1 ARs dominate, thus vasoconstriction occurs to increase venous return to the heart.

Front 24

How does epi affect bronchial smooth muscle?

Back 24

It binds B-2 ARs to cause relaxation and dilation of the bronchial passages.

Front 25

How do NE and epi affect the spleen? Which has the stronger effect?

Back 25

a-1 ARs are bind and cause contraction of the smooth muscle capsule of the spleen. This increases the number of blood cells in circulation.

Epi binds a-1 ARs with greater affinity, thus it has the stronger effect.

Front 26

How does adrenergic stimulation affect the uterus? Which plays the bigger role: epi or NE?

Back 26

Epi binds B-2 ARs to cause relaxation of the smooth muscle. NE does not bind with very high affinity.

Front 27

What effect does sympathetic innervation have on the seminal tract?

Back 27

a-1 ARs are activated and cause contraction of smooth muscle and constriction of the tract.

Front 28

What effect does sympathetic innervation have on the pupil?

Back 28

Activation of a-1 ARs in the ciliary radial muscles cause mydriasis (pupillary dilation).

Front 29

How can glaucoma be treated by B-1 antagonists?

Back 29

Blocking B-1 ARs in the ciliary epithelium inhibits the production of aqueous humor.

Front 30

How can glaucoma be treated with a-2 agonists?

Back 30

Binding a-2 agonists prevents further release of NE, thus decreasing B-1 activated production of aqueous humor by the ciliary epithelium.

Front 31

How can glaucoma be treated with B-2 agonists?

Back 31

Stimulation of B-2 ARs in the ciliary muscle will cause relaxation and increase outflow of aqueous humor.

Front 32

How is the hypertensive effect of NE release accentuated by the kidney?

Back 32

NE binds JG cells in the kidneys and stimulates release of renin which raises BP.

Front 33

What kind of AR are found in the pili erector muscles?

Back 33

a-1 ARs which causes conttraction when stimulated.

Front 34

Describe the sympathetic innervation of sweat glands.

Back 34

99% are innervated by postganglionic sympathetic neurons which release ACh.

1% are innervated by postganglionic sympathetic neurons which release NE that binds a-1 ARs.

Front 35

How does adrenergic stimulation reduce sympathetic outflow at the level of the medulla? What are two drugs that induce a hypotensive effect by action at at this level?

Back 35

NE binds a-2 ARs which inhibits further release of NE and decreases sympathetic outflow.

Clonidine and aldomet are a-2 agonists selective to these receptors.

Front 36

What are the net cardiovascular effects of isoproterenol?

Back 36

Activates B-1 ARs in the heart and B-2 ARs in the vascular smooth muscle. The net effects are:
*increased heart rate
*increased CTY
*increased systolic BP
*decreased diastolic BP
*increased pulse pressure

Front 37

What are the net cardiovascular effects of NE?

Back 37

Binds B-1 ARs in the heart to directly increase HR and CTY. Binds a-1 ARs in the vascular smooth muscle to cause vasoconstriction. Increased BP triggers the baroreceptor reflex and an indirect decrease in the heart rate through vagal stimulation is seen. Net effects are increased BP and decreased HR.

Front 38

What are the net cardiovascular effects of NE in a patient pre-treated with atropine?

Back 38

Atropine is a muscarinic blocker which inhibits vagal transmission in the heart. Net effects are increased BP and HR.

Front 39

What net cardiovascular effects are seen with NE given to a patient treated with an a-1 antagonist?

Back 39

This blocks the vasoconstrictive effect thus only increased heart rate is seen.