neurotransmitter and receptors

Question 1

what are the 5 criteria of neurotransmitters

Answer 1

1. in terminal
2. Ca2+ dependent release
3. subject to inactivation
4. synaptic mimicry
5. receptors exist

Question 2

how are amino acid NT the workhorses of the CNS

Answer 2

• predominant type of NT
• 90% of synapases involve 4 AA - glutamate, aspartate, GABA, or glycine

Question 3

whats the overall role of AA NT

Answer 3

can be excitatory (Glu, Asp) or inhibitory (GABA or Gly)

Question 4

AA NT receptors

Answer 4

• most work through ionotropic (ion channel) receptors
• some use metabotropic receptors

Question 5

AA NT inactivation

Answer 5

rapid uptake

• back into vesicle
• in glial cell - can stay there or go back to neuron

Question 6

what is glutamate

Answer 6

• major excitatory NT
• widely distributed through the CNS

Question 7

glutamate receptors

Answer 7

• ~13 types of receptors
• metabotropic - at least 8 varieties
• ionotropic - 3 major classes

Question 8

what are the 3 major classes or ionotropic glutamate receptors

Answer 8

• NMDA
• AMPA
• Kainate

Question 9

which ionotropic glutamate receptor is of the greatest interest and why

Answer 9

NMDA b/c it is heavily involved in learning and memory

Question 10

What is GABA

Answer 10

• major inhibitory NT in CNS
• widely distributed through the CNS (important in inhibitory control of interneurons)

Question 11

what is the name of the enzyme used to synthesize GABA

Answer 11

glutamic acid decarboxylase (GAD)

Question 12

what are the two families of GABA receptors

Answer 12

• GABA(A) receptors
• GABA(B) receptors

Question 13

GABA(A) receptors

Answer 13

allow Cl- ions into neuron resulting in membrane hyperpolarization

Question 14

GABA(B) receptors

Answer 14

• G-protein coupled
• connected to K+ channels to cause membrane hyperpolarization

Question 15

AA NT location importance

Answer 15

drugs acting on these transmitters/their receptors can exert GLOBAL effects on overall CNS function

Question 16

what is increasing the overall INHIBITION of the CNS useful for

Answer 16

sedation, anethesia, anxiolytics, seizure control

• ketamine
• benzodiazepines and barbiturates (enhance GABA(A) receptor)

Question 17

what is the enzyme used to synthesize acetylecholine

Answer 17

choline acetyletransferase

Question 18

how is acetylecholine inactivated

Answer 18

acetylcholinesterase (breaks down ACh)

Question 19

what are the two types of ACh receptors

Answer 19

• nicotinic Ach receptor (ionotropic)
• muscaromoc ACh receptor (metabotropic)

Question 20

location of cholinergic neurons

Answer 20

specific circuits throughout brain

Question 21

what are some CNS functions of ACh

Answer 21

• behavioral arousal
• attention
• REM sleep
• memory
• learning aggression
• grand mal seizures
• sensory perception
• energy conservation
• mood
• motor coordination

Question 22

Ach is a prominent NT of the:

specific nervous system

Answer 22

autonomic nervous system

Question 23

what is the action of acetylecholinesterase inhibitors

Answer 23

excessive buildup of ACh in the synapse is dangerous!

Question 24

what are acetylecholinesterase inhibitors - irreversible inhibitors (organophosphates)

Answer 24

many products used in industry and agriculture (and war)

• insecticides
• poisonous gases

poisoning is very common

• physiologic excess of AChE exist in the body
• profound effects when 80-90% of enzyme is inactivated
• exposure is cumulative
• many agents penetrate skin

Question 25

what is myasthenia gravis

Answer 25

an autoimmune disease with decreasing numbers of nicotinic receptors at neuromuscular junction

Question 26

what are the 3 types of catecholamines

Answer 26

* dopamine * norepinephrine * epinephrine

Question 27

what is a type of indoleamines

Answer 27

serotonin and melatonin

Question 28

what is the catecholamine precursor

Answer 28

tyrosine

Question 29

what is the rate limiting step and nonsecific decarboxylase of catecholamine synthesis

Answer 29

tyrosine 5-hydroxylase; aromatic amino acid decarboxylase

Question 30

what are the enzymes needed to make norepinephrine and epinephrine

Answer 30

dopamine-B-hydroxylase; phenylethanolamine-N-methyl transferase

Question 31

what is the rate limiting step in serotonin synthesis

Answer 31

tryptophan

Question 32

what are the rate-limiting steps and nonspecific decarboxylase for serotonin synthesis

Answer 32

tryptophan 5-hydroxylase; aromatic amino acid decarboxylase

Question 33

what are the rate-limiting steps in breakdown of catecholamines and serotonin and what is the same nonspecific enzyme? what is the additional enzyme needed for catecholamine breakdown

Answer 33

monoamine oxidase; aldehyde dehydrogenase; catechol-O-methyl transferase

Question 34

what are the two MAO subtypes

Answer 34

MAO-A and MAO-B

Question 35

preferences of MAO

Answer 35

* both subtypes capable of metabolizing all catecholamines and serotonin * serotonin, norepinephrine, and epinephrine broken down by MAO-A * dopamine broken down equally by both MAO-A and MAO-B

Question 36

MAO is a ____ enzyme and is ____ the mechanism for removal of monoamines from the synapse

Answer 36

mitochondrial, NOT

Question 37

catecholamine and indoleamine inactivation

Answer 37

rapid reuptake via specific transporters

Question 38

dopamine: location and function

Answer 38

* hypothalamic regulation of hormones * substantia nigra to basal ganglia play major role in movement * midbrain projections to cortex and limbic system involved in schizophrenia, central "reward" pathway, working memory

Question 39

what is parkinsons disease and how is it characterized

Answer 39

* progressive neurodegenerative disorder * fatigue, lethargy, changes inmental alertness, tremors, bent posture, difficulty initiating voluntary movement

Question 40

what does a marked loss of dopaminergic neurons in substantia nigra do

Answer 40

signs of parkinson's disease

Question 41

norepinephrine: location and function

Answer 41

* role in attention * involvement with control of feeding * connection to mood * cell bodies of NE neurons reside in pons and medulla (locus coeruleus LC, lateral tegmental area LTA, dorsal medullary DM)

Question 42

serotonin: location and function

Answer 42

* distribution in the body * 90% present in the enterochromaffin cells of the GI tract

Question 43

serotonin: location and function - CNS

Answer 43

* Raphne nuclei: all CNS serotonin is in the raphe and projects widely throughout * fire in a highly regulated, pacemaker-like manner

Question 44

what does the neuroanatomy and firing pattern of serotonin imply

Answer 44

broad homeostatic functions

Question 45

what is the main function of serotonin

Answer 45

mood

Question 46

what has low serotonin been associated with

Answer 46

* depression * panic * anxiety * obsessive-compulsive behaviors

Question 47

what is a drug used to tx low serotonin

Answer 47

Prozac - selective serotonin reuptake inhibitor (SSRI)

Question 48

what do SSRI do

Answer 48

inhibiting SERT prolongs action of serotonin (5-HT) in synapse