Pbd 2 Exam 2 (Peris)

Front 1

Where are central neurotransmitters synthesized?

Back 1

In the terminals

Front 2

Where are central neurotransmitters stored?

Back 2

In the terminals, two types:

Long-Term storage: not readily accessible
Short-term storage: readily available

Front 3

What are the two methods of neurotransmitter release?

Back 3

Vesicular - calcium dependent
Non-Vesicular - not calcium dependent

Most drugs target non-vesicular release

Front 4

What are your fast receptors for neurotransmitters?

Back 4

ligand-gated ionophores

excitation (EPSP) - depolarizes postsynaptic neuron
inhibition (IPSP) - hyperpolarizes postsynaptic neuron

Front 5

What are your slow receptors for neurotransmitters?

Back 5

membrane-bound enzymes
G-couples receptors

Front 6

What tasks do the slow receptors for neurotransmitters perform?

Back 6

1) Modulates signals of fast neurotransmitters
2)Can change hyperpolarization or depolarization
3) Regulate RNA transcription and protein translation

Front 7

What are your really slow receptors for neurotransmitters?

Back 7

Intracellular receptors - receptor is inside the nucleus of the cell

Front 8

What tasks do the really slow receptors for neurotransmitters perform?

Back 8

regulate RNA transcription and protein translation

Front 9

What are the mechanisms for rapid removal of neurotransmitters?

Back 9

Metabolism - enzymes
Reuptake - transporter proteins, involved in recycling the neurotransmitter

Front 10

Why are presynaptic receptors autoreceptors?

Back 10

They induce negative feedback and inhibit themselves

Front 11

What are the functions of fast receptors?

Back 11

Control membrane potential and ionic composition

Front 12

What commonly lines the center of the fast receptors?

Back 12

M2 subtype, located in the second spanning region

Front 13

Where does GABA bind on the GABAa receptor?

Back 13

Between the alpha and beta subunits

Front 14

Where do benzodiazepines bind on the GABAa receptor?

Back 14

Between the alpha and gamma subunits

Front 15

What does binding of a benzodiazepine to the GABAa receptor cause?

Back 15

It does not activate (open/close) the channel, it changes the shape of GABA binding allowing for higher potency with lower doses of GABA.

Allows Cl into the cell, leading to IPSP and sedation

Front 16

Why is benzodiazepine sedation safe?

Back 16

It is self limiting to the concentration of GABA in the body.

Front 17

How many regions does the g-protein-coupled receptor span?

Back 17

7 membrane spanning regions

Front 18

What is a G-protein?

Back 18

Protein made of 3 subunits (Beta, Gamma, and alpha)

Front 19

Which subunits of the G-protein are bound?

Back 19

Beta and Gamma

Front 20

Where is the alpha subunit of the G-protein located?

Back 20

Bound to the other subunits (Beta and Gamma) or free floating

Front 21

What occurs when the alpha subunit of the G-protein is released?

Back 21

It becomes activated, GDP becomes GTP, and the alpha subunit then binds to an effector

Front 22

What does the G-protein interact with?

Back 22

The loop between the membrane span of 5 and 6 of the G-protein-coupled receptor.

Front 23

What does Go do?

Back 23

Inhibits calcium channels

Front 24

What does Gs do?

Back 24

Activates calcium channels

Activates Adenylate Cyclase to increase cAMP production by converting ATP to cAMP.

cAMP then activates Protein Kinase A

Front 25

What does Gi do?

Back 25

Activates potassium channels

Inhibits Adenylate Cyclase to decrease cAMP production.

Activates phospholipase A2 (PLA2)

Front 26

What does Gq activate?

Back 26

Phospholipase C

Front 27

What is phospholipase C?

Back 27

Activated by Gq to make inositol triphosphate (IP3) and diacylglycerol (DAG) from PIP2.

Front 28

What is IP3?

Back 28

Created from PIP2 via PLC and stimulates the IP3 receptor on the calcium storage vesicle to release calcium into the cell.

Calcium then activates Protein Kinase C and other Calcium dependent protein kinases.

Front 29

What is DAG?

Back 29

Created from PIP2 via PLC and activates Protein Kinase C

Front 30

What is CREB?

Back 30

Cyclase response element - activated by Protein Kinase A.

Travels into the nucleus where it modulates DNA transcription and RNA translation.

It is this action that makes the G-coupled receptors both slow and really slow.

Front 31

What does PLA2 do?

Back 31

Phospholipase A2 liberates arachidonate from the membranes.

Arachidonate can then be broken down via 2 pathways: Cyclooxygenase type 1 or 2 and Lipoxygenase

Front 32

Detail the cyclooxygenase pathway

Back 32

Arachidonic Acid is broken down into PGG2 via cyclooxygenase 1 and 2. PGG2 becomes PGH2 which then is broken down into:

1) PGE2, PGF2, and PGD2
2) PGI2 via Prostacyclin synthase
3) TXA2 via Thromboxane synthase

Front 33

Detail the Lipoxygenase pathway

Back 33

Arachidonic acid is broken down to 5-HPETE via lipoxygenase. 5-HPETE becomes LTA4 which is then broken down into LTB4, LTC4, LTD4, and LTE4.

Front 34

What are some examples of really slow receptor stimulators?

Back 34

Steroid hormones, fatty acids, anything lipid soluble.

Front 35

How do the really slow receptors operate?

Back 35

Interact with the response element to activate or inhibit mRNA transcription.

Front 36

What is the rate limiting step for glutamate?

Back 36

Glutaminase

Front 37

How is glutamate reabsorbed?

Back 37

Na-dependent transporters specific for glutamate, located on both the glial cells and neurons.

Front 38

What are the receptors for glutamate?

Back 38

kainate, NMDA, AMPA, and metabotropic.

Front 39

What is the NMDA receptor?

Back 39

Excitatory receptor for glutamate that is coupled to an ionophore for Calcium, Na, and Potassium.

Potassium exits, Na and Ca enters.

Front 40

What is the AMPA receptor?

Back 40

Excitatory receptor for glutamate that is coupled to an ionophore for Na and Potassium. Potassium exits and Na enters.

Front 41

What is the Kainate receptor?

Back 41

Excitatory receptor for glutamate that is coupled to an ionophore for Na and Potassium. Na enters and Potassium exits.

Kainate is also the autoreceptor on the neuron for glutamate

Front 42

What is the metabotropic receptor?

Back 42

Also called the G-coupled receptor, stimulates the creation of IP3 and cAMP.

Front 43

How does the glial cell aid in glutamine uptake?

Back 43

The glial cell helps remove glutamate from the cell, converts it to glutamine via glutamine synthase. Glutamine is then added back to the neuron.

Front 44

How does glutamate affect learning?

Back 44

Long-term potentiation, hippocampal NMDA receptors activated when two or more neurons are simultaneously firing.

Front 45

What affects does glutamate have on the CNS?

Back 45

learning, excitotoxicity, epilepsy, and motor control/

Front 46

How does glutamate affect epilepsy

Back 46

Excess excitation and depolarization in the foci caused by glutamate.

Front 47

How is glutamate linked to excitotoxicity?

Back 47

Excessive glutamate release during reperfusion of blood following a stroke leads to NMDA/kainate stimulation and an increase in intracellular Ca. Excessive Ca leads to cell swealling and cell death.

Front 48

What is the cortico-striatal pathway?

Back 48

Goes from the motor cortex to caudate putamen. Stimulates (initiates) movement.

An important pathway for glutamate.

Front 49

Where are glutamate neurons, kainate, and AMPA receptors located in the brain?

Back 49

Everywhere, ha.

Front 50

What is the rate limiting step in the synthesis of GABA?

Back 50

Glutamic acid decarboxylase

Front 51

What is the GABA-A receptor?

Back 51

A ligand-gated ionophore for chloride with multiple subtypes of:

alpha (6)
gamma (3)
beta (4)
Also delta, epsilon and rho subunits.

Front 52

What effects does GABA have on the CNS?

Back 52

anxiety, sedation, epilepsy, and motor function

Front 53

How does GABA affect anxiety?

Back 53

Decreases locus ceruleous output and inhibits the amygdala and hippocampus

Front 54

How does GABA affect sedation?

Back 54

GABA inhibits neuronal firing

Front 55

How does GABA affect epilepsy?

Back 55

Inhibits neuronal hyperactivity in the foci and the substantia nigra inhibits the colliculi

Front 56

How does GABA affect motor function?

Back 56

5 of 6 cerebellar neurons are GABAergic. Caudate/putamen inhibits globus pallidus and the substantia nigra via GABA

Front 57

What is Huntingtons chorea?

Back 57

degeneration of striatal GABA neurons, results in excessive movement

Front 58

How does the glial cell convert GABA to glutamine?

Back 58

GABA is converted to glutamate via GABA transaminase. Glutamate is then converted to glutamine via glutamine synthase.

Front 59

What are the two GABAergic pathways?

Back 59

Striatum to substantia nigra and substantia nigra to colliculi

Front 60

What is the rate limiting step in norepinephrine synthesis?

Back 60

tyrosine hydroxylase

Front 61

What is DBH?

Back 61

Dopamine Beta-Hydroxylase, converts dopamine into norepinephrine. If DBH is not present, then the cell is a dopamine cell.

Front 62

What is tyrosine hydroxylase?

Back 62

The rate limiting enzyme in the formation of DOPA from tyrosine.

Front 63

What is DOPA?

Back 63

Product of the breakdown of tyrosine by tyrosine hydroxylase. It is converted to dopamine by decarboxylation.

Front 64

What receptors does NE stimulate?

Back 64

Alpha-1, Alpha-2, and Beta

Front 65

What is the alpha-1 receptor?

Back 65

Stimulated by NE and Gq linked, results in the activation of PLC and an increase in IP3 and DAG.

Front 66

What is the alpha-2 receptor?

Back 66

Stimulated by NE and Gi linked to inhibit adenylate cyclase and stimulate G-coupled potassium channels.

Also linked through Go to inhibit calcium channels.

Alpha-2 also serves as the autoreceptor for NE.

Front 67

What is the Beta receptor?

Back 67

Stimulated by NE and Gs linked to stimulate adenylate cyclase.

Front 68

In what forms is NE metabolized?

Back 68

Majority of NE is metabolized by MAO-A in the neuron.

Some NE is metabolized by MAO-B in the glial cells.

NE may also be metabolized by COMT into an inactive metabolite.

Front 69

How does NE affect the nucleus tractus solitarius?

Back 69

NE stimulates alpha-2 receptors in the nucleus tractus solitarius and increases the baroreceptor reflex, resulting in decreased blood pressure.

Front 70

Where are most norepinephrine cell bodies located?

Back 70

In the locus ceruleus in the midbrain, but it branches throughout.

Front 71

What is the reticular activating system?

Back 71

Regulates alertness and part of the ascending NE system.

Front 72

What is the descending NE pathway involved in?

Back 72

Pain transmission

Front 73

What do opoids do?

Back 73

Increases enkephalin in the spinal cord, which results in decreased pain transmission.

Front 74

What is the rate limiting step in serotonin synthesis?

Back 74

Dietary tryptophan levels

Front 75

How is serotonin metabolized?

Back 75

Neuronal MAO-A

Front 76

What are the serotonin receptors?

Back 76

5-HT1, 5-HT2, 5-HT3, 5-HT5, 5-HT4,6,7

Front 77

What is 5-HT1?

Back 77

Serotonin receptor linked to Gi that inhibits cAMP and stimulates potassium channels

Front 78

What is 5-HT2?

Back 78

Serotonin receptor linked to Gq that activates PLC

Front 79

What is 5-HT3?

Back 79

Serotonin receptor linked to a ligand-gated ionophore for sodium and potassium

Front 80

What is 5-HT4, 6, 7?

Back 80

Serotonin receptor linked through Gs to stimulate cAMP

Front 81

What is What is 5-HT5?

Back 81

Serotonin receptor linked to Gi, resulting in decreased cAMP

Front 82

What is likely to occur if an agent that acts as an antagonist to serotonin release is taken?

Back 82

Increased sensory information and hallucinations

Front 83

How does serotonin affect pain transmission?

Back 83

Increases enkephalin in the spinal cord and decreases pain

Front 84

Where are the serotonin cell bodies located?

Back 84

In the raphe nuclei, with projections throughout the brain

Front 85

What is the area postrema chemoreceptor trigger zone?

Back 85

Leaky area of the blood brain barrier that detects products in the blood that will alter neurotransmission. If the product exists 5-HT3 is stimulated to induce vomiting.

Front 86

Which serotonin receptor is involved in migraines?

Back 86

5HT1D on the cranial blood vessels

Front 87

Which serotonin receptor is involved in emesis?

Back 87

5HT3 in the area postrema

Front 88

Which serotonin receptor is involved in psychosis?

Back 88

5HT2 in the prefrontal cortex and NAc

Front 89

Which serotonin receptor is involved in anxiety/depression?

Back 89

5HT1A in the hippocampus and amygdala

Front 90

How does serotonin affect inhibiting pain?

Back 90

caudral RAS to lamina II spinal cord

Front 91

How does serotonin affect inhibiting sensory transmission?

Back 91

Rostral RAS to thalamus and cortex

Front 92

How does serotonin affect sleep/arousal?

Back 92

Rostral RAS to cortex and hypothalamus

Front 93

What acts as the autoreceptor for serotonin?

Back 93

Alpha-2

Front 94

What is the rate limiting step in the synthesis of dopamine?

Back 94

Tyrosine hydroxylase

Front 95

How is dopamine metabolized?

Back 95

MAO-A, MAO-B, COMT

Front 96

What are the dopamine receptors?

Back 96

D1, D2, D3, D4, D5

Front 97

What is D1?

Back 97

Inhibitory receptor for dopamine, linked to Gs and increases cAMP

Front 98

What is D2?

Back 98

Inhibitory receptor for dopamine, linked to Gi, decreases cAMP and Potassium

Front 99

What is D3?

Back 99

Dopamine receptor that commonly forms a heterodimer

Front 100

What is D4?

Back 100

Dopamine receptor linked to Gi, decreases cAMP

Front 101

What is D5?

Back 101

Dopamine receptor that increases cAMP

Front 102

What is the autoreceptor for dopamine?

Back 102

D2 and D3

Front 103

What receptors are located in the chemoreceptor trigger zone?

Back 103

Alpha 2 and D2

Front 104

What are the dopaminergic pathways?

Back 104

1) Substantia nigra to caudate/putamen
2) Ventral tegmental area to nucleus accumbens/Prefrontal cortex
3) Hypothalamus to pituitary gland

Front 105

What occurs if you utilize a D2 blocker?

Back 105

Too little dopamine, too much ACh and too much GABA. Results in Hypokinesia, rigidity and tremors (Parkinson's like symptoms)

Front 106

What occurs if you have too much dopamine?

Back 106

Too little ACh, too little GABA, results in hyperkinesia and chorea (Huntington's disease)

Front 107

What is the rate limiting step in the synthesis of ACh?

Back 107

Choline uptake

Front 108

How is ACh metabolized?

Back 108

Acetylcholinesterase converts ACh into choline (which can be reabsorbed) and acetate.

Front 109

What are the receptors for ACh?

Back 109

M1, M2, M3, M4, N

Front 110

What is the M1 receptor?

Back 110

Excitatory ACh receptor that is linked through Gq to activate PLC (increases DAG and IP3)

Front 111

What is the M2 receptor?

Back 111

Inhibitory ACh receptor that is linked through Gi to decrease cAMP and Potassium

Front 112

What is the M3 receptor?

Back 112

Excitatory ACh receptor that is linked through Gq to activate PLC (increases DAG and IP3)

Front 113

What is the M4 receptor?

Back 113

Inhibitory ACh receptor that is linked through Gi to decrease cAMP and Potassium

Front 114

What is the N receptor?

Back 114

Excitatory ACh receptor that is linked to a ligang-gated ion channel. Increase Na and Calcium, decreases Potassium.

Front 115

What are the cholinergic pathways?

Back 115

1) Short interneurons in caudate/putamen
2) Basal nucleus to frontal and parietal cortex and thalamus
3) Septal nucleus to hippocampus
4) Pons to thalamus and hypothalamus