Neuropeptides

Question 1

Peptide Hormones vs. Neuropeptides

Answer 1

o Neuropeptides – act on nearby cells; vary in length from 3-36 amino acids
o Peptide hormones – act on distal cells/tissues

Question 2

Major Differences in Synthesis of NT and Neuropeptides

Answer 2

o Neuropeptides synthesized from mRNA in neuron/glial cells; neurotransmitters are produced from AA and have rate limiting step enzymes

Question 3

Fast Amino Acid Neurotransmitter Characteristics

Answer 3

– glutamate, GABA, glycine –
 Stored in clear synaptic vessels and released BEFORE neuropeptides
 Fast vesicle recycling
 Ultra short distance
 Ionotropic receptors
 Low frequency stimulation causes release

Question 4

Slow Neuropeptide Transmission

Answer 4

– hypocretin, NPY, MCH, POMC, vasopressin, dynorphin, substance P – modulate neural activity
 Stored in large dense core vesicles and released AFTER AA NT release
 Slow vesicle recycling
 Local diffusion
 Can bind to G-protein coupled receptors; or modulate other receptors
 High frequency stimulation causes extra-synaptic release – not in synaptic cleft

Question 5

Neuropeptide Transmitter Functions

Answer 5

• pain, appetite, cardio/respiratory, GI, reward, fear, locomotion, immune suppressors, mood, pleasure, pain, weight, and energy

Question 6

Opioid Peptides

Answer 6

o Enkephalins – peptide neurotransmitter; reduces pain
 4 conserved amino acid sequence; additional AA form different enkephalins
o Endorphins – endogenous morphine; reduces pain
 Same 4 conserve AA sequence as enkephalins and therefore part of enkephalin family
 Less strong  bind with less affinity to opioid receptor and degrade faster
 Beta-endorphins – released from brain during exercise and reduce the intensity of pain
o Dynorphin

Question 7

Substance P and NAAG

Answer 7

• Substance P – modulates pain

* NAAG – smallest neuropeptide (2 amino acids)

Question 8

Neuropeptide Processing

Answer 8

o Prohormone convertase 1 and 2 – endoproteolysis between basic residues
o Carboxypeptidase E – exoproteolysis of C-terminal basic residue
o Aminopeptidase – exoproteolysis of N-terminal basic residue
o Amidation of C-terminal glycines
o Acetylation of N-terminal

Question 9

ACTH Processing

Answer 9

Pre-proopiomelanocortin (w/ signal peptide bound) –> proopiomelanocortin + signal peptide –> ACTH + beta-lipotropin –> gama-lipotropin + beta-endorphin

Question 10

Calcitonin Genes

Answer 10

– different splicing mechanisms results in either calcitonin or CGRP
o Calcitonin – thyroid cells – involved in calcium metabolism
o CGRP – brain – involved with pain and vasodilator
o Neuropeptides – unique in that a given gene can give rise to a protein and a neuropeptide with completely different biological profiles

Question 11

Clearance, Renewal of Neuropeptides

Answer 11

o Extracellular degradation by endo- and exopeptidases

o Renewal of neuropeptides relies on synthesis in the cell body

Question 12

Neuropeptide Receptors

Answer 12

– G protein receptors with 7 transmembrane domains
 Varying affinity for neuropeptides since some are not as stable as others
o Bradykinin: B1, B2
o Opiods – mu, delta, kappa

Question 13

Neuropeptides can be Co-localized with NT

Answer 13

– released by the same neuron
o NPY – Norepinephrine – locus ceruleus
o Dynorphin – GABA – striatum
o CCK – dopamine – striatum
o Somatostatin – GABA – striatum
o VIP – ACh – parasympathetic post-ganglion
o CGRP – ACh – spinal motor
o Neurotensin – dopamine – substantia nigra
o Thyrotropin-releasing hormone (TRH) increases GABA-mediated transmission
o NPY inhibits glutamate action

Question 14

Neuropoietic Cytokines

Answer 14

– help in producing neurons, oligodendrocyte, astrocytes from stem cell
o Interleukins 6 and10
o Leukemia inhibitory factors (LIF)
o Neuropoietin and cardiotrophin like cytokines

Question 15

Neuropoietic Receptors

Answer 15

o Extracellular domain + Intraceullular domains which activate JAK-STAT and MAPK pathways

Question 16

Neuropoietic Cytokines Function/Involved in:

Answer 16

o	CNS development, neurogenesis
o	Neuronal/glial survival
o	Neuroinflammation
o	Activate responses after CNS injury
o	Stress responses
o	Participate in chronic pain

Question 17

Pro-inflammatory cytokines

Answer 17

– not expressed in brain unless there is inflammation
o Interleukin-1
o Tumor necrosis factor

Question 18

Chemokines

Answer 18

– neuroinflammatory modulators
o Induce chemotaxis in nearby responsive cells
o Considered pro-inflammatory and can be induced during an immune response to promote cells of immune system to a site of infection
o Exert biological effects by interacting with G protein-linked transmembrane chemokine receptors

Question 19

Cytokines vs. Chemokines

Answer 19

o Cytokines – provide support for neuronal differentiation

o Chemokines – modulate responses to injury

Question 20

Response to Injury

Answer 20

– monocyte chemoattractant protein 1 (MCP1) or CCL2 will attract monocyte/macrophages

Question 21

Neurotrophic Factors and Functions

Answer 21

– small proteins that exert survival-promoting and trophic actions on neuronal (or nerve) cells; active in both CNS and PNS
 Neuronal differentiation
 Neuronal survival and maintenance
 Neuronal repair/plasticity
o Include neurotrophins, neuropoietic cytokines, glial-cell derived NTFs, fibroblast growth factors, and insulin-like growth factors

Question 22

Important Neurotrophins

Answer 22

o Nerve growth factor (NGF) – sympathetic and sensory neuron maturation; cholinergic neurons in brain; auditory neurons in inner ear; development of visual system
o Brain-derived neurotrophic factor (BDNF) – increases dendritic spine density

Question 23

Biological Functions of Neurotrophins

Answer 23

o	Multiple neurons of the CNS
	Basal forebrain acetylcholine – memory 
	Nigro-striatal dopamine – movement
	Serotonin – anxiety, food intake
	Cortical glutamate – movement
	Cortical noradrenergic – depression
o	Auditory neurons of inner ear
o	Development of the visual system

Question 24

Neurotrophin Receptors Activated by Nerve Growth Factor (NGF)

Answer 24

o Trks (tropomyosin-receptor-kinase) – high affinity receptors – induce cell survival, differentiation, and synaptic plasticity
o P75 – a low affinity receptor –induce cell death
 Involves Pro-neurotrophins
 Involved with injury