test 4 part 2

Question 1

Adrenergic receptor locations

Answer 1

• effector organ from adrenal medulla

- NE from post synaptic symp neuron on effector organ

Question 2

Sympathetic Nervous System

Answer 2

 Norepinephrine (Noradrenaline)
 Primary neurotransmitter released by adrenergic
neurons
 CNS
 Sympathetic nervous system
 Epinephrine (Adrenaline)
 Released from adrenal medulla as a hormone

Question 3

adrenal medulla releases

Answer 3

• 80% epinephrine

- 20% NE

Question 4

Sympathomimetics

Answer 4

-mimic sympathetic NS
 Drugs that activate adrenergic receptors
 Direct-acting agonists
 Indirect-acting agonists (effect amount of NE present)

Question 5

Sympatholytics

Answer 5

 Drugs that block the activation of adrenergic receptors

Question 6

Adrenergic Neurotransmission step 1

Answer 6

• Tyrosine is transported into neuron and hydroxylated to dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
• DOPA is decarboxylated into dopamine in the presynaptic neuron
-hydroxylation of tyrosine is the rate-limiting step

Question 7

Adrenergic Neurotransmission step 2

Answer 7

• Dopamine transported into vesicles by amine transporter system
• Dopamine is hydroxylated to Norepinephrine by dopamine β-hydroxylase
-takes place inside the vessicle

Question 8

Adrenergic Neurotransmission step 3

Answer 8

• Action potential arrival triggers influx of Calcium ions
• Synaptic vesicles fuse with cell membrane
• Exocytosis releases contents into synapse

Question 9

Adrenergic Neurotransmission step 4

Answer 9

• NE binds to postsynaptic receptors on effector organ (or to autoreceptors on nerve ending)
• Metabotropic receptors trigger cascade of events within the cell
• Intracellular second messengers transduce the signal

Question 10

Adrenergic Neurotransmission step 5

Answer 10

• Norepinephrine is removed from synaptic space

    1. Diffuses out
    2. Is taken back into neuron
    3. Metabolized by catechol-O- methyltransferase (COMT) in the synaptic space

Question 11

Adrenergic Neurotransmission step 6

Answer 11

• Norepinephrine is
1. Taken up into synaptic vesicles
2. Persists in cytosol
OR
3. Oxidized by monoamine oxidase (MAO)

Question 12

Adrenoreceptors

Answer 12

 Two main families (α and β) classified by their affinities for norepinephrine, epinephrine, and isoproterenol (a direct acting synthetic catecholamine)

Question 13

α-Adrenoreceptors

Answer 13

 Potency and affinity
-Affinity:
epinephrine > norepinephrine&raquo_space; isoproterenol

Question 14

α-Adrenoreceptors

Answer 14

 Subdivided into 2 groups based on their affinities for α agonists and antagonists
 α1 – relatively high affinity for phenylephrine
 α2 - relatively high affinity for the anti-hypertensive drug clonidine

Question 15

α1

Answer 15

 Postsynaptic membrane of effector organs
 Mediate many classic adrenergic effects of smooth muscle (constriction)
 Activates G proteins to form second messengers
 DAG: turns on other intracellular proteins
 IP3: initiates release of calcium from endoplasmic reticulum into cytosol

Question 16

α1 Effect

Answer 16

• agonist binds causing the GDP to fall off and GTP to bind to the alpha subunit
• disassociates and activates phospholipase C
• Phospholipase C then uses second messengers DAG and IP3 leading to an increase in intracellular Ca++

Question 17

What happens when you stimulate an α1 receptor

Answer 17

 Increased vascular tone → increased SVR → increased blood pressure
 Mydriasis (pupils dilate)
 Increased bladder tone
 Increased tension in prostate

Question 18

α1 Logic

Answer 18

 Think… “Fight or Flight”
 You want an increase in blood pressure
 You want to take in as much light as possible
 You don’t want to stop and urinate

Question 19

α2

Answer 19

 Primarily on sympathetic presynaptic nerve endings
 Also found on parasympathetic presynaptic nerve endings
 Control release of norepinephrine: inhibitory autoreceptors- create negative feedback loops
 Effect mediated by inhibition of adenylyl cyclase and decrease in cAMP

Question 20

α2 Effect

Answer 20

-activation of alpha 2 receptor decreases production of cAMP leading to an inhibition of further release of nerepinephrine from the neuron

Question 21

What happens when you stimulate an α2 receptor

Answer 21

 Inhibition of norepinephrine release
         Inhibition of sympathetic tone in vasculature (decrease BP)
 Inhibition of ACh release
 Inhibition of insulin release
 sedative for anesthesia

Question 22

α Receptors location

Answer 22

 α1 – postsynaptic membrane of effector organ

 α2 - presynaptic nerve endings

Question 23

α Receptor Subdivisions

Answer 23

 α1
further divided into A, B, C and D
 α2
further divided into A, B, and C
 Necessary for understanding selectivity of certain drugs
-reason we care is that we can give drugs that don’t affect all of the alpha receptors

Question 24

β-Adrenoreceptors affinity

Answer 24

isoproterenol > epinephrine > norepinephrine

-synthetic substance, not found endogenously

Question 25

β-Adrenoreceptor

Answer 25

 Subdivided into 3 major subgroups based on affinities for β agonists and antagonists - adrenergic receptors so they use a G protein and function via second messengers - any time you stimulate a beta receptor you have an increase in cAMP

Question 26

β-Adrenoreceptor Subtypes

Answer 26

 β1  Equal affinity for norepinephrine and epinephrine (both much less than isoproterenol)  β2  Higher affinity for epinephrine than norepinephrine  β3  Involved in lipolysis and have effects on the muscle of the bladder

Question 27

The heart contains predominately

Answer 27

β1 receptors

Question 28

What happens when you stimulate a β1 receptor

Answer 28

 Tachycardia  Increased myocardial contractility  Increased renin release from kidneys (increase BP)  Increased lipolysis

Question 29

β1 Logic

Answer 29

 Heart beats harder and faster to deliver more blood to skeletal muscle  More triglycerides for energy  Increased blood pressure for increased tissue perfusion

Question 30

β2 found mostly where

Answer 30

- in the lungs

Question 31

What happens when you stimulate a β2 receptor

Answer 31

```  Relaxation of pulmonary smooth muscle  Vasodilation of skeletal muscle  Decreased PVR  Increased glucagon release  Uterine muscle relaxation ```

Question 32

β2 Logic

Answer 32

 Airways open for more oxygen  More blood flow to skeletal muscle  More glucagon for energy

Question 33

α1 mostly affects

Answer 33

vasculature

Question 34

α2 mostly affects

Answer 34

CNS feedback loops to treat HTN and provide sedation

Question 35

β1 mostly affects

Answer 35

the heart

Question 36

β2 mostly affects

Answer 36

the lungs

Question 37

Dopaminergic Receptors

Answer 37

 5 subtypes exist  D1 and D2 in peripheral mesenteric and renal vascular beds  D2 on presynaptic adrenergic neurons  Dopamine can affect all other adrenergic receptors  Main sites of action of dopamine  Brain  Renal and visceral arterioles  Cardiovascular system -G protein receptors -interfere with release of NE

Question 38

Dopamine Logic

Answer 38

 Renal  Vasodilation  Natriuresis  Cardiac  Activates β receptors of the heart and increases contractility and rate  Vascular  Can increase or decrease PVR in a dose dependent manner

Question 39

Receptor Desensitization

Answer 39

 Prolonged exposure to the catecholamines (NE, epi, and dopamine) reduces the responsiveness of the receptors  Sequestration of receptors (become unavailable for binding)  Down-regulation  Phosphorylation of receptor – inability to couple G protein