NTs and receptors

Question 1

what are the two classes of NTs?

Answer 1

1. small molecule NTs - Ach, glutamate, A.A, purines, biogenic amines
2. Peptide NTs - >100, usually 3-30 aa

Question 2

which one is the first NT to be identified and which one is the major excitatory NT in the CNS?

Answer 2

1. first NT to be identified - Ach

2. glutamate

Question 3

what is the difference b/w excitatory and inhibitory A.A NTs?

Answer 3

excitatory - 2 negative charges atphysiological pH

inhibitory - 1 negative charges at physiological pH

Question 4

Glycine despite being inhibitory NT, it is co-agonist for NMDA class of Glutamate receptors 
True or False

Answer 4

True

co transporters are usually a combination of +ve and -ve

Question 5

name the following

1. what is GABA synthesised from?
2. it is loaded into synaptic vesicles via what?
3. it is cleared by what?

Answer 5

1. Synthesised from Glutamate by glutamic acid decarboxylase (GAD)
2. Loaded into synaptic vesicles by VIAAT
3. Cleared by GATs (GABA transporter 1) – Na+-dependent co-transporters

Question 6

what are the two types of GABA receptors?

Answer 6

1. GABAA ionotropic – Cl- channels

2. GABAB metabotropic- activate K+ channels or inhibit Ca2+ channels

Question 7

where are GABAaR agonists used?

Answer 7

GABAA R agonists widely used sedatives, anxiolytics, anti-convulsants, anaesthetics

Question 8

what is the difference b/w barbiturates and benzodiazepine?

Answer 8

• barbiturates activates GABAa

- benzodiazepine enhances GABAa

Question 9

give an example of barbiturates and benzodiazepine

Answer 9

barbiturates - pentobarbital benzodiazepine - diazepam

Question 10

give an example where GABAa inhibitor is used?

Answer 10

Inhibitors (e.g. picrotoxin, PTZ) used experimentally as convulsants – animal models of epilepsy

Question 11

give examples of GABAaR antagonists and where it is used?

Answer 11

1. bicucilline - in the labs

2. flumazenil - used clinically for BZD (benzodiazepine) overdose

Question 12

give examples of GABAbR agonists and where it is used?

Answer 12

Baclofen – spasticity - to make the muscles more relaxed

Question 13

give examples of GABA reuptake inhibitors (GRI) and where it is used?

Answer 13

tiagabine/ Gabitril – anxiety, epilepsy

Question 14

give examples of GABA analogues and where it is used?

Answer 14

GABA analogues e.g. gabapentin – seizures & neuropathic pain

Question 15

name the conditions that result due to less or more inhibition

Answer 15

less inhibition - arousal, epilepsy, death

more inhibition - sleep, coma, death

Question 16

GABA is excitatory in early development - True or False justify

Answer 16

True
embryo - High NKCC1 -> High [Cl-]I -> GABA -> Cl-efflux Depolarising
adults - High KCC1 -> Low [Cl]I -> GABA -> Cl-influx Hyperpolarising

Question 17

which is the main inhibitory NT in spinal cord and brainstem?

Answer 17

glycine

Question 18

where is glycine

1. synthesised from
2. loaded into synaptic vesicles via what
3. how is it cleared?

Answer 18

1. Gly synthesised from Ser by serine hydroxyl-methyltransferase
2. Loaded into synaptic vesicles by VIAAT
3. Cleared by specific GlyT – mutations give hyperglycinemia (lethargy, seizures, MR)

Question 19

what can the mutation in glycine transporter result in?

Answer 19

mutations give hyperglycinemia (lethargy, seizures, mental retardation)

Question 20

what type of receptors are glycine?

Answer 20

ionotropic, Cl- channels

Question 21

name a substance that inhibits glycine and what can that result into?

Answer 21

inhibited by strychnine – induces seizures

Question 22

what are the characteristics of purines?

Answer 22

• ATP excitatory NT in CNS & PNS – MNs, sensory and autonomic ganglia
• ATP rapidly catabolised to adenosine
• Ionotropic receptors for ATP (P2X), metabotropic receptors for ATP (P2Y) and adenosine (P1)

Question 23

Adenosine is a NT

True or False

Answer 23

False, it does not meet the criteria of NT (able to pack into vesicles and release upon Ca2+ activation)

Question 24

what is the function of purinergic receptors?

Answer 24

• Modulators:- neuroprotective agents?- chronic pain?

- Non-CNS functions, e.g. P2Y12 inhibitors anti-platelet agents

Question 25

name a few biogenic amines

Answer 25

Catecholamines – dopamine, norepinephrine/noradrenaline, epinephrine/adrenaline Imidazoleamine - histamine Indoleamine – serotonin (5-hydroxytryptamine)

Question 26

outline the catecholamine biosynthesis

Answer 26

L-tyrosine -> L-DOPA -> DOPAMINE -> L-Noradrenaline -> L-adrenaline

Question 27

what is the function of dopamine and what diseases are related to them?

Answer 27

1. movement - PD 2. Motivation, reward & enforcement - drug addiction 3. cognition and emotion

Question 28

what are the dopaminergic pathways?

Answer 28

1. SN to striatum – initiation of movement 2. VTA-Nac – reward pathway – addictive behaviour 3. VTA – MCP – limbic – cingulate gyrus – cognitive, emotion and motivation

Question 29

in which disease is MAO-B and COMT inhibitors used?

Answer 29

- MAO-B and COMT catabolise dopamine - MAO-B inhibitors (Selegiline & Rasagiline) used early PD - COMT inhibitors (e.g. Entacapone & Tolcapone) used with Levodopa in PD

Question 30

what type of receptors are dopamine receptors and what are its classes?

Answer 30

All metabotropic i.e. G protein coupled | 2 classes:- D1-like via Gs- D2-like via Gi

Question 31

which substance inhibits the removal of dopamine by DAT?

Answer 31

cocaine

Question 32

how dopamine receptors subtypes are present?

Answer 32

- D1-D5 | - D2/3/4 – targeted by anti-psychotics

Question 33

what is major source and function of NA?

Answer 33

``` major source - locus coeruleus function - sleep, wakefulness and attention ```

Question 34

where is adrenaline produced?

Answer 34

- mainly medullary epinephrine neurons in the medulla

Question 35

adrenergic beta blockers are used to terra what?

Answer 35

β-blockers, e.g. propranolol used to treat cardiac arrhythmias & migraines

Question 36

what is the function of histamine?

Answer 36

has role in attention and arousal

Question 37

what are the features of histamine?

Answer 37

- Lots of peripheral effects e.g. allergies - Located in tuberomammillary nucleus (in the hypothalamus) - 3 classes – H1-3 CNS relevance – can cross - the BBB – could be effective sedatives - Promethazine - may cause drowsiness (beyond a sedative for him)

Question 38

what are the function of serotonin? (5-HT)

Answer 38

- function - Mood, sleep, wakefulness, nausea, appe

Question 39

what is the clinical significance of 5-HT?

Answer 39

- loss of 5-HT in depression - therefore, targets for anti-depressants and anxiolytics to increase it - since 5-HT is cleared by SERT - drugs like SSRI - fluoxetine/prozac target them

Question 40

why are the down sides of too much 5-HT?

Answer 40

XS serotonergic agonism → serotonin syndrome, range from mild (shivering & diarrhea) to severe (rigidity, fever & seizures) non-CNS - constipation

Question 41

all of the 7 5-HT are metabotropic except one, name it

Answer 41

5-HT3 - inotropic

Question 42

how are the 5-HT agonists and antagonists targeted in diseases?

Answer 42

5-HT agonists - migraine | 5-HT antagonists - nausea/vomiting (chemotherapy), withdrawn diet pill (fen-phen)

Question 43

outline the role of peptide NTs in diseases and its function

Answer 43

1. Pain – substance P & opioid peptides 2. Stress responses – CRH/CRF 3. Food intake – NPY, melanocortins 4. Pituitary peptides – vasopressin, oxytocin 5. Hypothalamic-releasing peptides – LHRH

Question 44

what is the significance of HPA axis?

Answer 44

- Mediates stressresponses | - dysfunction - associated with psychiatric disorders