Flashcards in Week 8 Glutamates, opiates, neuropeptides, anandamines, and neuromodulators Deck (14)
Describe the biosynthesis and recycling of glutamate (GLU) and aspartate (Asp).
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
Give a general description of glutamate receptors
-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
Describe AMPA receptors.
-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
Describe Kainate receptors
-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
Describe NMDA receptors.
-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
What is the mechanism of phencyclidine (PCP)?
-compete with regulatory Mg2+ binding site of NMDA receptor
-lower concentrations: psychotomimetic, causing delusions, hallucinations, cognitive defects
-higher doses: dissociative anesthetic effects
Dinoflagellates and MSG act on which receptors?
-dinoflagellates red tide: NMDA antagonist
What are the agonists and antagonists of opiate receptors?
-mixed function: pentazocine
Describe the biosynthesis of endogenous opiates.
-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
Describe the opioid receptors.
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
Describe the mode of action of opiates.
-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
-nociceptin and nocistatin: pain perception
-tachykinins: includes substance P (capsaicin induces release of substance P, low dose =hyperalgesia, high=analgesia)
-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