NT-metabolism III- Salmen

Question 1

steps of histamine metabolism

Answer 1

1. Histidine is converted to histamine by the enzyme histidine-decarboxylase (HDC)
2. histamine
3. histamine can be broken down into 3 products:
   a. Imidazoleacetylaldehyde by the enzyme Diamine-oxydase –> other metabolites
   b. acetyl-histamine
   c. methyl-histamine by the enzyme histamine-methyltransferase (HMT) –> other metabolites

Question 2

the pathways of histamine to the brain are…(which statements are correct?)

a. Histamine is synthesised in the anterior hypothalamus (tubero-mammilary nucleus-TMN)
b. Histamine is synthesised in the posterior hypothalamus (tubero-mammilary nucleus-TMN)
c. Histamine producing neurons in the hypothalamus fire during states of sleep
d. Histamine producing neurons in the hypothalamus fire during states of wakefulness and arousal to other parts of the brain and periphery
e. histamine is synthesised in the brainstem

Answer 2

b, d

Question 3

what histamine receptors can you name, and what is their localisation, and affiliated G protein? bonus- agonists/antagonists of the receptors (example)

Answer 3

• H1 : Gq/11, localisation- cortex, hippocampus, nucleus accumbent, thalamus; no selective agonist; antag.: mepyramine, triprolidine
• H2: Gs, localisation- BG, hippocampus, amygdala, cortex; agonist- Dimaprit; antag.: cimetidine
• H3: Gi/o, localisation- BG, hippocampus, cortex; agonist- R-alpha-methylhistamine; antag.: Thioperamide

Question 4

when feeling itchy….(which of the following statements is correct?)

a. Itch is a sensation mediated by the H1 receptor
b. cGRP KO mice have shown reduced itchiness
c. Itch is a sensation mediated by the H3 receptor
d. histamine binds to H1 receptor on the primary afferent nociceptors in the periphery –> cGRP and substance p release–> signal to the brain and spinal cord

Answer 4

a, b, d

Question 5

what are the steps of neuroactive peptides synthesis?

Answer 5

1. pre-peptide gene
2. pre-peptide mRNA
3. preps-tide
4. propeptide

Question 6

steps of pain processing (from periphery to brain)

Answer 6

1. Tissue damaging stimulus activates nociceptors (periphery)
2. message carried to spinal cord
3. descending pathway
4. message received in the thalamus and cortex

Question 7

how do opiates relieve pain?

Answer 7

1. opioids act on opioid receptors in the DESCENDING pathway, which is the analgesic pathway.
2. the activation of opioids receptors in this pathway suppresses nociceptor activity (which are activated following a tissue damage)

Question 8

what is the difference between primary nociceptors and dorsal horn nociceptors?

Answer 8

dorsal horn nociceptors have a lot more receptors than primary nociceptors.

primary nociceptive neuron: u, alpha-2 and CB1 receptors- not on active zone of synapse

dorsal horn neuron- on AZ; cGRP, Nk1, AMPA, u, TrkB

Question 9

what are the key enzymes in ACh synthesis

Answer 9

1. Choline + Acetyl CoA –> synthesis of ACh + CoA by enzyme choline-acetyl-transferase
2. CoA is then taken up to produce acetyl CoA
3. ACh is degraded to choline + acetate by the enzyme ACh esterase –> acetate transformed to acetyl and Acetyl CoA is produced.