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Physiology and Pharmacology > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

What are ligand-gated ion channels involved in?

A

Fast synaptic transmission (microseconds - millisecond)

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2
Q

What are endogenous ligands?

A

Fast/classical neurotransmitters

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3
Q

What are examples of neurotransmitters?

A

glutamate, ACh

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4
Q

How many subunits are in ligand-gated ion channels?

A

3-5

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5
Q

How many transmembrane spanning domains are in each subunit?

A

2-4

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6
Q

How is the complex arranged to form?

A

a central aqueous pore

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7
Q

What are structural features of ligand-gated ion channel families?

A 
cys-loop structure
many distinct nicotinic receptors
many, many distinct GABAa receptors
two distinct 5-HT3 receptors (Nicotinic-5 domains)
two distinct glycine receptors
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8
Q

What are three main classes of ligand gated ion channels?

A
  1. nicotinic ACh receptor
  2. glutamate receptor
  3. P2X receptor
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9
Q

What is an example of a ligand-gated ion channel?

A

nAChR

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10
Q

Where is nAChR found?

A

Neuromuscular junction, CNS, PNS

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11
Q

What is the agonist for nAChR?

A

nicotine

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12
Q

What is the antagonist for nAChR?

A

tubocuranine (nicotinic receptors blocked in neuromuscular junction) can lead to asphyxiation

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13
Q

What does the activation of ionotropic receptors for inhibitory neurotransmitters lead to?

A

Inhibit membrane depolarization

Reduce action potential firing

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14
Q

What is an example of an activation of ionotropic receptors for inhibitory neurotransmitters?

A

GABAaR

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15
Q

Where is the GABAaR found?

A

brain

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16
Q

What are agonists for GABAaR?

A

GABA, phenobarbitone

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17
Q

What is an antagonist for GABAaR?

A

Picrotoxin

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18
Q

What is phenobarbitone used for?

A

euthenasia

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19
Q

What does phenobarbitone do?

A

Opens all inhibitory GABA receptors in brain to inhibit CNS activity which can lead to a coma which leads to death

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20
Q

What can picrotoxin lead to?

A

Excitation and inhibition
convulsion
epileptic seizures

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21
Q

What are examples of endogenous ligands?

A

vasopressin, angiotensin

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22
Q

What is an example of neuropeptides?

A

opioids

23
Q

What are examples of small molecule transmitters?

A

ACh, nonadrenaline, histamine

24
Q

What are examples of metabolic receptors?

A

mAChRs, adrenoceptors, opioid receptors

25
Q

How many times does the receptor polypeptide span the membrane?

A

7 times

26
Q

Is it formed from multiple subunits?

A

no

27
Q

What protein does it use to regulate effector proteins?

A

G proteins

28
Q

What does a G protein generate?

A

Second messenger

29
Q

Are signals by G protein coupled receptors long-lasting or short?

A

Long

30
Q

What sort of processes are G protein coupled receptors involved in?

A

gene transcription

31
Q

Are G proteins heterotrimeric or homotrimeric?

A

heterotrimeric

32
Q

What are G proteins?

A

Proteins that bind guanine nucleotides (GDP at rest and GTP when activated)

33
Q

What are the three subunits of G-proteins?

A

alpha, beta, gamma

34
Q

Which subunits split when activated?

A

alpha, beta-gamma

35
Q

What does it mean when the subunits dissociate and the receptor is free?

A

The receptor is free to activate more G proteins for amplification

36
Q

How many major families of G-protein alpha-subunits are there?

A

4

37
Q

What does Gs(alpha) do?

A

Increase AC activity and cholera toxin sensitive

38
Q

What do Gi1(alpha), Gi2(alpha), Gi3(alpha), Go(alpha) do?

A

Increase AC activity and is pertussis toxin sensitive

The beta-gamma subunits bind directly to Ca and K subunits

39
Q

What do Gt1(alpha), and Gt2(alpha) do?

A

Initiate cG phosphodiesterase cascade (visual transduction)

40
Q

What does PLC activate?

A

PKC

41
Q

What does Gq(alpha) activate?

A

PKC and PLC

42
Q

What effectors are regulated by G protein coupled receptors (GPCRs?)

A

enzymes which regulate levels of second messengers

ion channels

43
Q

What are examples which regulate levels of second messengers?

A

Gs : increases adenylyl cyclase and cAMP
Gi : decreases adenylyl cyclase and cAMP
Gq : increases PLC, IP3 and intracellular calcium

44
Q

Can single GPCRs regulate multiple effectors?

A

yes

45
Q

Can multiple GPCRs couple to a single effector?

A

yes

46
Q

Is there cross-talk between receptors?

A

yes

47
Q

_ of extracellular changes

A

intracellular coding

48
Q

What are examples of GPCRs involved in the regulation of catecholamine in the cardiovascular system?

A

beta-1 adrenoceptors, positive ionotropic and chronotropic effects in the heart
alpha-2 adrenoceptors, presynaptic inhibition of NA release

49
Q

What can adrenoceptor agonists be used for in the cardiovascular system?

A

Adrenaline - cardiac arrest
adrenaline - anaphylaxis
Clonidine - hypertension

50
Q

What can adrenoceptor agonists be used for in the respiratory system?

A

Salbutamol (beta-2 selective) - bronchodilator

Ephedrine (beta agonist indirectly acting sympathomimetic drug which causes NA release) - nasal decongestant

51
Q

What are clinical uses for adrenoceptor antagonists?

A

prazosin (alpha 1 selective) - hypertension
carvedilol (alpha and beta) - heart failure
Propanolol (beta 1 and beta 2) - anxiety (somatic symptoms)

52
Q

What are unwanted effects from adrenoceptor antagonists?

A 
bronchoconstriction
cardiac depression (elderly)
bradycardia
fatigue
cold extremities
53
Q

How can drugs act indirectly to enhance cholinergic transmission?

A

Inhibits cholinesterase
e.g. acetylcholinesterase (AChE)
CSF, synaptic cleft at cholinergic synapses and cholinergic nerve terminals

54
Q

How are anticholinesterease drugs classified by duration of action?

A 
Short acting (reversible binding): edrophonium
Medium (slow hydrolysis): neostigmine and pyridostigmine  (MG don't cross BBB), physostigmine (crosses BBB - used topically for glaucome)
Long (irreversible): nerve gas, organophosphates, pesticides (crosses BBB)

Physiology and Pharmacology (27 decks)

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