L20 Neurotransmitters

Question 1

What are the four general classes of NTs?

Answer 1

1. small molecule transmitters - ACh and serotonin
2. neuropeptides - CCK, substance P, VIP, orexin (vasopressin + oxytocin)
3. gases - CO, NO

Question 2

what is the life cycle of NT?

Answer 2

• synthesis
  
  • nerve ending cytoplasm - small mole. NT
  • in rER, Golgi and vesicles - neuropeptides
  • in synap. vesicles - NE from DA
• storage in vesicles
• release
• binding to receptors
• degradation/re-uptake/reabsorption/diffusion

Question 3

All NTs (with the exception of ACh, NO and peptides) are removed rapidly via _______ in the nerve ending by glial cells

Answer 3

transporters

*example - glutamate is taken up by neurons _ taken into astrocytes by their glutamate transporters. Glutamate is metabolized into glutamine which has its own transporter in neurons

Question 4

DA, E, NE and serotonin are absorbed then broken down by ___ from the outer mitochondrial membrane in the nerve ending

Answer 4

MAOs

• there is also some degradation from COMT
• MAO and COMT are also present in astrocytes in liver
• some extracellular sites for MAO do exist.

Question 5

what receptors do cholinergic neurons (ACh) use?

Answer 5

ionotropic - nicotinic

metabotropic - muscarinic

Question 6

muscarinic M1, M3 and M5 have what type of response?

Answer 6

slow excitatory response - Gq–>PLC -> IP3 +DAG increase –> increase [Ca2+]

Question 7

Muscarinic M2 and M4 have what type of responses?

Answer 7

inhibitory responses - Gi –> cAMP decrease –> closure of Ca2+ channels = weaker sponataneous depolarization

Question 8

what are the major muscarinic subtypes in the brain (cerebral cortex + hippocampus)?

Answer 8

M1, M3, M4

Question 9

what muscarinic subtype mediates gastric acid secretion?

Answer 9

M1

Question 10

what type of actions do catecholamines (E, NE, and DA) have

Answer 10

both excitatory and inhibitory

Question 11

what type of receptors do catecholamines use/

Answer 11

metabotropic only

Question 12

where is DA important

Answer 12

CNS - parkinsons disease

no role in PNS

Question 13

where is NE released from and what does it activate?

Answer 13

postganglionic sympathetic neurons

adrenoceptors in smooth n., glands and cardiac m.

Question 14

where is E released from and what does it activate?

Answer 14

chromaffin cells

enters circulation and activates adrenoreceptosr

Question 15

what isoproterenol?

Answer 15

synthetic form of epinephrine - similar in sutrcture to adrenaline (E), but has an additional CH3 group on the terminal N

Question 16

where do dopaminergic cells in the substantia nigra project?

Answer 16

basal ganglia striatum (caudate nucleus + putamen)

D1 and D2 receptors on striatal neurons

Question 17

where do dopaminergic neurons in the ventral tegmental area project?

Answer 17

hippocampus - new memory formation
nucleus accumbens
frontal lobe cortex - planning and attitude

Question 18

how many receptors does DA have

Answer 18

5

Question 19

what are the 2 families of DA receptors?

Answer 19

D1 - like (D1 and D5) - increase cAMP (excitatory)

D2-like (D2, D3, D4) - inhibit cAMP

Question 20

what do postganglionic sympathetic neurons do to cardiac muscle?

Answer 20

excite!

Question 21

what is the function of cardiac muscles beta 1 receptors?

Answer 21

increase cAMP - excite the HR and pacemaker

Question 22

cardiac output increases in response to what stimulation?

Answer 22

sympathetic

Question 23

what type of channels are AMPA/kainate and NMDA?

Answer 23

cation

Question 24

describe the AMPA receptor

Answer 24

typical Na+ channel

Question 25

describe the NMDA receptor

Answer 25

- blocked by residing Mg2+ which leaves under influence of very large depolarization (due to summation of many EPSPs) - when it is unblocked it allows Ca2+ entry into the postsynaptic cell where the calcium plays a role in alterations of enzyme activity

Question 26

what neurotransmitters mediate synaptic inhibition

Answer 26

glycine and GABA

Question 27

what is the main inhibitory NT in the spinal cord

Answer 27

glycine

Question 28

how does the glycine work in the spinal cord?

Answer 28

ionotropic receptor selective to Cl- - has similar structure to nAChR but NEEDS 3 MOLECULES OF GLYCINE TO OPEN CHANNEL!

Question 29

how many molecules of glycine must bind to nGlyR?

Answer 29

3

Question 30

what is the main inhibitory transmitter in the brain stem and brain?

Answer 30

GABA

Question 31

what does GABAa receptor resemble

Answer 31

nAChR and glycine receptors - with two molecules of transmitter binding to alpha subunits before it can open!

Question 32

how many molecules of GABA need to bind to GABAa receptor

Answer 32

2

Question 33

what kinds of substances to glycine and GABA receptors bind?

Answer 33

anti-epileptic drugs, anti-anxiety drugs, sedatives, muscle relaxants, anesthetics

Question 34

describe GABAb receptors?

Answer 34

metabotropic receptos - indirectly cause K+ channel opening through 2nf messengers - slow inhibition of postsynatpic neuron

Question 35

how do benzodiazepines and barbiturates act on GABAa receptor channels?

Answer 35

-inhibition in the amygdala invovled with the development of fear and anxiety

Question 36

where is the binding site on GABAa for benzos?

Answer 36

gamma subunit

Question 37

where is the binding site on GABAa for barbiturates?

Answer 37

alpha and beta subunits

Question 38

cholinergic neurons in the septal nuclei, basal nucleus of Myenert and pons connect to maintain ______, regulating a high level of consciousness

Answer 38

peak excitability

Question 39

what do the ascending arousal system and cholinergic neurons also participate in?

Answer 39

raising levels of consciousness during REM sleep

Question 40

amines and peptides have crucial roles in what

Answer 40

the CNS

Question 41

the neurons in the locus ceruleus and rostral raphe nuclei innervate neurons in the

Answer 41

limbic lobe and cortex - mood, LO anxiety and optimism

Question 42

when NE and serotonin transmission is low...

Answer 42

mood = feelings of despair, fear, anxiety

Question 43

what does DA play a role in

Answer 43

depression and schizophrenia

Question 44

what are brain dopamine receptors target in tx od

Answer 44

schizophernia, parkinsons disease and huntingtons chorea

Question 45

dopamine receptor antagonist block what

Answer 45

- neuroleptics - block hallucinations and delusions

Question 46

dopamine receptor agonists alleviate signs of what disease

Answer 46

-bromocriptine - sings of parkinsons disease

Question 47

what therapeutic drugs are used to tx clinical depression

Answer 47

1- SSRI - slow upreg of serotonin receptors 2. noradrenaline reuptake inhibitors 3. MAO inhibitors - reduce degradation of NE and serotonin

Question 48

what are the 3 endogenous opiod peptide families?

Answer 48

1. beta endorphins 2. enkephalins 3. dynorphins *they inhibit pain

Question 49

what does substance P do

Answer 49

information about tissue damage and substance P mediates the increased pain sensation

Question 50

what is capsaicin

Answer 50

in red hit chilli peppers - analgensic for pain = desensitize receptors and pain is reduced prolonge capsaicin admin. downreg pain caused by death of primary afferent neurons = decreased release of substance P

Question 51

what is the MOA for pilocarpine?

Answer 51

mimics ACh - agonist for muscarinic receptors of PNS

Question 52

what is pilocarpine used to tx?

Answer 52

glaucoma - facilitates fluid drainage from eye via canal of Schlemm

Question 53

what is the MOA for beta blockers

Answer 53

anatagonists of beta 1 receptors used to treat htn

Question 54

what receptors do asthmatic bronchodilators work?

Answer 54

beta 2 agonist

Question 55

what receptors do nasal decongestants work on

Answer 55

alpha 1 agonist = phenlephrine