4. Acetylcholine and co

Question 1

acetylcholine synthesis

Answer 1

acetyl co A and choline by ChAT - choline acetyl transferase which is used for histological staining

Question 2

acetylcholine breakdown

Answer 2

cholinesterases into constituents in synapse and then reuptaken

Question 3

ACh CNS structures:

Answer 3

magnocellular forebrain (nucleus basalis of meynertand septohippocampal pathway) and the brainstem (pedunculopontine  and laterodorsal tegmentum)
also striatal interneurons in rats but not humans (for movement)

Question 4

what is ACh for?

Answer 4

attention and arousal

Question 5

ACh CNS structures are

Answer 5

species dependent - rats ave striatal interneurons that we don’t have

Question 6

Septohippocampal pathway

Answer 6

projects from the forebrain to the hippocampus - is important in short term memory and learning

Question 7

NbM

Answer 7

Projects to the cotrex and also to the inhibitory layer of cells just above the thalamus - thalamic reticular nucleus - involved in general arousal

Question 8

brain stem ACh

Answer 8

sleep wake cycles (cholinergic input –> thalamus = wake state) and motor activity

Question 9

ACh receptors

Answer 9

nicotinic and muscarinic

Question 10

Nicotinic ACh receptors

Answer 10

pentamers (homo or heteromeric) - fast EPSPs - Na/K or Ca permeability changes - move large hydrophobic residues out of channel pore and replace with small aqueous residues to form a pore lining - usually presynaptic to facilitate glutamate release

Question 11

metabotropic ACh receptors

Answer 11

M1,3,5, - E (Change NA perm)
M2,4 - I (change K/Ca perm)
more widespread

Question 12

Excitatory mAchRs

Answer 12

use the M current. wont generate an AP on their own but a small sustained current instead. If a stimulus is applied during the M current it’ll fire a train of action potentials. it synaptic sensitivity.

Question 13

Histamine synthesis

Answer 13

synthesise from histadine by histadine decarboxylase (only 64000 cells)

Question 14

histamine metabolism

Answer 14

broken down by histmaine methyltransferase to methylhistamine and the broken down by MAO

Question 15

histamine projects to

Answer 15

thalamus!! cortex, amygdala, hypothalamus - the system is more developed in lower mammals - switch on and off in wake and sleep state (discrete)

Question 16

histamine in the body

Answer 16

stimulates release of bradykinin in response to damage

Question 17

H1

Answer 17

cAMP (E)

7TMDs GPCR

Question 18

H2

Answer 18

IP3 (E)

7TMDs GPCR

Question 19

H3

Answer 19

auto/heterocetor?

7TMDs GPCR

Question 20

histamine drugs: H1

Answer 20

Old ones used to be sedative but new ones can’t cross BBB - treat allergies and stings

Question 21

histamine drugs: H2

Answer 21

used to treat acidity and stomach ulcers - BBB impermeable

Question 22

histamine drugs: H3

Answer 22

analogues used to treat chronic dizziness in the vestibular system

Question 23

Neuropeptides SYNTHESIS

Answer 23

Always in the soma but can be transported to the terminal as a co-molecule or in its active form

Question 24

Neuropeptides NT’S?

Answer 24

vesicualr release, ca dependent, act on GPCRs but no obvious fast actions - only slow modulatory effects
but co transmission

Question 25

co-transmission

Answer 25

neuropeptides released alongside other NTs to extend their maximal effects (e.g. salivary glands, VIP only released at high freq. firing to extend ACh action) However some places have NTs as primary form of transmission

Question 26

Purines

Answer 26

e.g. adenosine (ATP) can be released (free of vesicles) as a soup to act on A1/2/2B/3 - more protective than transmissive - prevents hyperexcitability - acts on same system as caffeine. produced de novo.

Question 27

Melatonin

Answer 27

produced in the pineal gland fro serotonin - acts on MT1/2 in the retina and brain - synthesis stimulated by night and day- used to treat depression, ADHD and jetlag

Question 28

NO

Answer 28

Nitric oxide is produced in response to elevates ca levels (de novo) by NOS (NO synthase) and released paracrinally - effecting cells up to 400um away - it can have both inhibitory and excitatory effects (seconds to minutes)

Question 29

roles of NO

Answer 29

co transmitter in PPT pathway of ACh. LTP and neurotoxicity (from excitabiity)

Question 30

name the lipid transmitters:

Answer 30

endocannabinoids (2AG and anadamide) Eicosanoids, protsalglandins and leukotrienes.

Question 31

lipid NT transmission and synthesis:

Answer 31

retrograde transmission both auto and paracrinally. They can modulate glutamate and gaba release. Cell signalled and arachadonic acid formed from part of the membrane. this converted into EC/Ei which are then released to act on presynaptic cells.

Question 32

EC receptors

Answer 32

CB1/2 are used in the treatment of pain and nausea. they can alter both glutamate and gaba release through retrograde signalling