Week 8 Glutamates, opiates, neuropeptides, anandamines, and neuromodulators

Question 1

Describe the biosynthesis and recycling of glutamate (GLU) and aspartate (Asp).

Answer 1

Glu and Asp are major excitatory neurotransmitters, especially glu.

• synthesized in the brain and released in Ca2+ dependent manner from synaptic vesicles (Ca influx cause release of synaptic vesicles)
• reuptake: amino acid transporters, ion gradients, and ATP needed. Glial cells also collaborate in recycling

Question 2

Give a general description of glutamate receptors

Answer 2

• gated ion channels or G protein coupled
• 3 families of glu receptors: AMPA, Kainate, NMDA (N-methyl D aspartate)
• agonist increase ion channels’ tendency to open

Question 3

Describe AMPA receptors.

Answer 3

• receptors made of 16 different subunits, various pentameric forms
• structures determine receptors desensitization rate
• allow inward flow of Na+ and outward flow of K+
• overexcitement can lead to neuronal death (caused by rush of Ca2+ ions)
• AMPA receptors found in striatum, hippocampus, cerebellum

Question 4

Describe Kainate receptors

Answer 4

• agonist-Kainic acid (KA)-bind with high affinity
• high levels kill these neurons
• neuro-active endogenous steroids effective in protecting against KA induced seizures in mice

Question 5

Describe NMDA receptors.

Answer 5

• voltage sensitive
• regulated by Mg2+ ions inside ion channels, must be displaced by membrane depolarization.
• permeable to Na, Ca, and K once Mg is dispaced
• Glycine is an essential co-agonist
• associated with spacial learning and learning capacity

Question 6

What is the mechanism of phencyclidine (PCP)?

Answer 6

• Angel’s dust
• compete with regulatory Mg2+ binding site of NMDA receptor
• lower concentrations: psychotomimetic, causing delusions, hallucinations, cognitive defects
• higher doses: dissociative anesthetic effects

Question 7

Dinoflagellates and MSG act on which receptors?

Answer 7

NMDA

-dinoflagellates red tide: NMDA antagonist

Question 8

What are the agonists and antagonists of opiate receptors?

Answer 8

• Agonist: morphine
• antagonist: naloxone
• mixed function: pentazocine

Question 9

Describe the biosynthesis of endogenous opiates.

Answer 9

• precursor to beta endorphin: pro-opiomelanocortin (POMC)
• precursor for met-enkephalin and leu-enkephalin: proenkephalin
• precursor for dynorphin: prodynorphin
• peptides are destroyed by specific peptizes

Question 10

Describe the opioid receptors.

Answer 10

3 major families: mu, kappa, delta

• most opiod analgesics used clinically bind to mu, also respiratory depressants
• codeine is low affinity mu receptor agonist
• mu: cAMP mediated potassium channel, reduces excitability and Ca2+ influx
• heroin overdose can be rescued by naloxone

Question 11

Describe the mode of action of opiates.

Answer 11

• inhibition of pain pathways includes presynaptic modulation of Substance P
• acupuncture, runner’s high, painless birth-may utilize enkephalins or endorphins
• SID increases in newborns whose mothers had opiate addiction (affects respiratory centers in brain stem)
• non-neuronal cells may have receptors for neuropeptides, e.g. immune system cells

Question 12

Other neuropeptides

Answer 12

• nociceptin and nocistatin: pain perception

- tachykinins: includes substance P (capsaicin induces release of substance P, low dose =hyperalgesia, high=analgesia)

Question 13

Describe anandamide.

Answer 13

• they are endogenous cannabinoids
• THC binds to cannabinoid receptors
• CB1 receptor found in CNS, CB2 has peripheral distribution and is expressed on leukocytes and testicles

Question 14

What is a neuromodulator?

Answer 14

• may not cause immediate change in membrane potential, but change membrane’s capacity to respond to further signals
• can tune membrane potential and their action is longer lasting. May induce a change in gene expression.
• e.g. nitric oxide