Exam #02 (General Info)

Question 1

Major peripheral effects for alpha-1 receptor

Answer 1

vasoconstriction, mydriasis (constricting the muscle dilates the pupil)

Question 2

Major peripheral effects for alpha-2 receptor

Answer 2

inhibit ACh, NE release (this inhibits sympathetic tone)

Question 3

Major peripheral effects for beta-1 receptor

Answer 3

stimulate HR and force of contraction

Question 4

Major peripheral effects for beta-2 receptor

Answer 4

relax respiratory, uterine, vascular skeletal muscle, stimulate glycogenolysis and insulin release

Question 5

Major peripheral effects for beta-3 receptor

Answer 5

stimulate lipolysis

Question 6

Major peripheral effects for D-1 receptor

Answer 6

dilation of renal blood vessels

Question 7

Synthesis pathway and release of NE at adrenergic synaptic junction

Answer 7

1. Tyrosine cotransported into cell with Na+
2. Tyrosine hydroxylase converts tyrosine to L-DOPA (rate-limiting step)
3. Dopa decarboxylase converts L-DOPA to DA
4. DA is transported into vesicle via VMAT (this would be the last step if this was a dopaminergic neuron)
5. DA hydroxylase converts DA into NE in the vesicle
6. AP traveling down the neuron, opens Ca+2 channels
7. Ca+2 causes vesicle to bind to presynaptic membrane and dump NE into synaptic cleft

Question 8

Fate of NE once dumped in synaptic cleft

Answer 8

1. It can bind to adrenergic 7TM-GPCR (alpha or beta)
2. it is metabolized by MAO and COMT
3. transported back into the neuron via NET (reuptake)
4. bind to autoreceptor

Question 9

NE Autoreceptor mechanism (include autoreceptor type)

Answer 9

Major negative feedback mechanism for NE. Autoreceptor is an alpha-2 receptor. NE binding to autoreceptor reduces NE release. NE is an agonist at the auto receptor, but has indirect antagonistic effects

Question 10

Main way NE is cleared from synaptic cleft

Answer 10

reuptake via NET

Question 11

2 drugs that block the NET and the effects it causes

Answer 11

cocaine and tricyclic-antidepressants
these drugs block the NET increasing NE conc. in synaptic cleft thereby increasing NE activity
So, these drugs are acting like indirect agonists

Question 12

Heteroceptor

Answer 12

binds different NT than one being released. Helps regulate the NT being released

Question 13

% of NE and Epi stored within the adrenal medulla

Answer 13

80% Epi

20% NE

Question 14

Where in adrenal medulla Epi and NE are stored

Answer 14

chromaffin granules (similar to vesicles)

Question 15

Where is NE methylated to form Epi?

Answer 15

in the cytoplasm

Question 16

Would NE released from adrenal medulla into blood be considered a NT or hormone?

Answer 16

hormone

Question 17

The rate of synthesis (NE –> Epi) is tightly tied to what steroid hormones secreted by the adrenal cortex?

Answer 17

glucocorticoids

Question 18

Stimulation of alpha-1 receptor by catecholamines leads to the activation of what G-protein?

Answer 18

Gq coupling protein

Question 19

Describe what the Gq protein goes on to activate once stimulated by binding of catecholamine to alpha-1 receptor and the 2nd messengers involved

Answer 19

the activated alpha-q subunit of the G-protein goes on to activate Phospholipase C which leads to the release of IP3 and DAG

Question 20

What function do the 2nd messengers released from alpha-1 receptor activation from catecholamine binding?

Answer 20

1. IP3 stimulates release of sequestered Ca+2 increasing cytoplasmic [Ca+2] which may activate Ca+2 dependent protein kinases
2. DAG activates protein kinase C (PKC)

Question 21

Binding of catecholamines to beta receptors leads to the activation of what G-protein?

Answer 21

Gs (stimulatory G-protein)

Question 22

Binding of catecholamines to alpha-2 receptor leads to the activation of what G-protein?

Answer 22

Gi (inhibitory G-protein

Question 23

Explain the cascade of events after activation of Gs?

Answer 23

1. Activation of Gs leads to dissociation of the G-protein’s alpha subunit charged with GTP
2. GTP-alpha subunit directly activates adenylyl cyclase which INCREASES [cAMP]

Question 24

Explain the cascade of events after activation of Gi?

Answer 24

1. Activation of Gi leads to dissociation of the G-protein’s alpha-i subunit charged with GTP
2. GTP-alpha-i subunit inhibits adenylyl cyclase which DECREASES [cAMP]

Question 25

Describe how activation of dopamine receptors (D1 - D5) affect 2nd messengers involved in each specific cascade?

Answer 25

Activation of D1 = INCREASE [cAMP]

Activation of D2 - DECREASE [cAMP], INCREASE K+ channels, DECREASE [Ca+2]

Activation of D3 - DECREASE [cAMP], INCREASE K+ channels, INCREASE [Ca+2]

Activation of D4 - DECREASE [cAMP]

Activation of D5 - INCREASE [cAMP]

Question 26

Would you mainly see vasoconstriction or vasodilation from activation of alpha-2 receptors?

Answer 26

you’ll mostly see vasodilation. However, some vasoconstriction can be observed but would occur ONLY if you inject a alpha-2 agonist into the veins and bypass the CNS and you would need a very high dose

Question 27

——— are drugs that mimic the actions of NE and Epi

Answer 27

Sympathomimetics