Histamine, Neuropeptides & Nitric Oxide

Question 1

Describe the function and distribution of histamine

Answer 1

Excitatory at some synapses and inhibitory at other synpse; median eminence and premamillary regions of the hypothalamus; these neurons project to almost all areas of the brain and spinal cord

Question 2

Describe the removal of histamine

Answer 2

Histamine methyltransferase and diamine oxidase (histaminase) metabolize histamine into organic aldehydes and acids, which are excreted in urine

Question 3

What is the synthesis of histamine?

Answer 3

Histidine iss decarboxylated by histidine decarboxylase to form histamine

Question 4

Summarize nuclei and projections

Answer 4

Nuclei and projections

The hypothalmic tuberomamillary nucleus (TMN)
constitutes the principal aggregation of histamine-producing neurons. Histaminergic efferents innervate the cortex, hypothalamus, posterior pituitary, cerebellum, medulla and spinal cord

Question 5

What are the histamine receptors?

Answer 5

• H1 receptors increase excitability by suppressing activity of potassium channels.
• H2 receptor activation stimulates protein kinase activation which inhibits calcium activated potassium channels.
• H3 receptors are negatively coupled to adenylate cyclase. Subunits of the G-protein also suppress voltage-gated calcium channels to decrease transmitter release.

Question 6

What are the metabotropic histamine receptors?

Answer 6

Metabotropic
– H1 and H2 Postsynaptic
• Excitatory, Promotes synaptic plasticity
– H3 Somatodendritic autoreceptor, Presynaptic
• Inhibitory autoreceptor or heteroreceptor (reduce neurotransmitter release)

Question 7

Describe the synthesis of Beta-endorphin

Answer 7

Originates from the pre-propeptide pre-proopiomelanocortin in the rough endoplasmic reticulum of the anterior and intermediate pituitary and the arcuate hypothalamic nucleus

b. Within the rough endoplansmic reticulum, the propeptide proopiomelanocortin arises
c. Proopionmelanocortin (POMC) undergoes packaging in the smooth endoplasmic reticulum
d. Fast orthograde transport drives vesicles from the hypothalamus to the periaqueductal grey and noradrenergic nuclei
e. Proteolytic cleaving yields beta- endorphin, among other peptides

Question 8

How is Beta-endorphin remived?

Answer 8

Degraded by peptidases

Question 9

Describe the function and distribution of Beta-endorphin

Answer 9

Inhibitory aat most synapses in the medulla and spinal cord

Opioid peptides are important participants in central pain-regulating pathways

Question 10

What are the mrtabotropic receptors of beta-endorphins?

Answer 10

Mu, delta, kappa, ORL1

Question 11

Describe the synthesis of Enkephalins

Answer 11

a. Originate from the pre- propeptide pre-proenkephalin in the rough endoplasmic reticulum of spinal and caudal bulbar neurons
b. The resultant proenkephalin undergoes packaging and fast orthograde transport
c. Proteolysis yields leucine - and methionine-enkephalin, which are then loaded into dense-core vesicles in preparation for exocytosis

Question 12

Describe the removal of Enkephalins

Answer 12

Degradation by peptidases

Question 13

Describe the function and distribution of enkephalins

Answer 13

Inhibitory at most synpses in the medulla and spinal cord

Question 14

What are the metabotropic for enkephalins?

Answer 14

Mu, delta, kappa, ORL1

Question 15

What receptors do opiod peptides use?

Answer 15

Metabotropic receptor- Mu, delta, kappa, ORL1

Question 16

Describe the synthesis of Substance P

Answer 16

An 11-amino acid peptide (tachykinin family) synthesuzed from a large precursor protein in the endoplasmic reticulum and transported to the nerve terminal

Question 17

Howw is substance P removed?

Answer 17

Degradation by peptidases

Question 18

What is the function & distribution 9f Substance P?

Answer 18

Excitatory at some synapses and inhibitiry at other synapses; widely distributed throughout the CNS

Question 19

What are the general principals of Nitric Oxide?

Answer 19

Nitric oxide (featured below) and carbon monoxide have been identified as diffusible intercellular messengers. They are thus considered as neurotransmitters, despite their failure to meet traditional criteria for transmitters.

1. Not stored in vesicles
2. Non-exocytotic
3. Inactivation is passive and spontaneous
4. No surface receptors
5. Retrograde transmission possible

Question 20

Describe the synthesis and removal of NO

Answer 20

Synthesis and Removal

• The mechanism for the synthesis of nitric oxide (NO) varies among tissues. Some neurons express a neuron-specific isoform
of nitric oxide synthase (cNOS), which triggers synthesis, as follows:
• 1. Glutamate activates post-synaptic NMDA receptors
• 2. Ca++ entering through the NMDA-related pore combines with calmodulin to activate cNOS
• 3. cNOS interacts with L-arginine to yield NO and L-citrulline
• 4. NO activates guanylate cyclase, promoting synthesis of cGMP in either the NO-expressing cell itself or, after intercellular diffusion, neighboring cells (neurons or glia)

Question 21

Whaat is the mechanism of NO?

Answer 21

Calcium enters cell
Calcium-calmodulin formed
NO activated
L-arginine cvvverted to L-citrulline and NO