neuronal function

Question 1

ACh synthesis and metabolism

Answer 1

Synthesised by choline O-acetyltransferaes in the cytosol. It is accumulated into vesicles by VAChT. Upon release metabolised by AChE, and choline is recovered back into the nerve by ChT.

Question 2

NA synthesis, reuptake and metabolism

Answer 2

Synthesised by dopamine beta-hydroxylate in the cytosol. Accumulated into vesicles by VMAT2. Upon release recovered by NET. IC metabolism by MAO and COMT.

Question 3

Presynaptic receptors function and examples

Answer 3

Inhibitor receptors found on the presynaptic cell. Autoreceptors bind to the NT released by the neurone it is found on. E.g., a2-AR.

Heteroreceptors are innervated by other neurones, and bind to a different NT. e.g., opioid receptors in GIT motility. High frequency stimulation of parasympathetic innervation of gut releases endogenous opioid peptides.

Question 4

Opioids receptor types and function

Answer 4

Opium - plant latex
Opiate - derived from opium plant
Opioid - any drug that binds opioid receptors

mu, kappa and delta receptors. mu for analgesia in CNS and periphery, delta for peripheral analgesia, and kappa for spinal analgesia.

Question 5

Enkephalins role and, therapeutic exploitation

Answer 5

Enkephalins are endogenous opioid peptides.

Neprilysin is a endopeptidase found in the gut that degrades enkephalin.

Thiorphan is a neprilysin inhibitor, previously used to treat diarrhoea.

Question 6

Opioid receptor signalling cascades

Answer 6

Gai subunit inhibits adenylyl cyclase to reduce cAMP.

Gai and betagamma subunits open K+ efflux channels (GIRK) - hyperpolarises cell.

Thus inhibits Ca influx through VGCC.

Question 7

TCA mechanism of actions

Answer 7

Treat neuropathic pain and depression/anxiety. E.g., amitryptaline.

Many targets: NET, SERT, DAT inhibitor. mAChR, histamine receptor, 5-HT2, and a1-AR antagonist.

Inhibits VGSCs.

Question 8

Endocannabinoids synthesis and receptors function

Answer 8

CB1: neuronal
CB2: immune (agonism -> antiinflammatory)

Endocannabinoids generated on demand, not vesicular. They are made from omega-3/6 fatty acids: lipophilic.

They can act on GPCRs, LGICs, and NHRs.

Question 9

Social interactions and endocannabinoids

Answer 9

The hypothalamic paraventricular nucleus (PVN), projects to the nucleus accumbens (NAc), and releases oxytocin following the social interaction. A post-junctional neurone between PVN and NAc (connects PVN and NAc) releases AEA (endocannabinoid), which agonises CB1 in the NAc. This associates reward with social interaction.

Question 10

Homeostasis of stress mediated by endocannabinoids

Answer 10

Hyperexcitation of glutamatergic signalling in stressful situations leads to heightened Gq-mediated (mGluRs) production of DAG. This DAG is then metabolised by DAGL to produce 2-AG, which is an endocannabinoid.

2-AG is effluxed out of the post-synaptic cell, and then acts on CB1 receptors found at the presynaptic cell, hyperpolarising it (GIRK mediated), thus reduce the glutamatergic signalling from the neurone.