neuropeptides Flashcards
true or false - there are more neuropeptides than neurotransmitters
true
neuropeptides are similar in design and function to peptide hormones in the ______ (what two systems)
pituitary and GI
polypeptide precursors are called what
propeptides and pre-propeptides
true or false - neuropeptides are bigger than proteins
false - they are smaller than proteins
where does peptide synthesis occur
in the cell body
what do pre-propeptides contain
a series of hydrophobic amino acids at the N-terminus
how is the signal sequence cleaved in pre-propeptide sequencing and what is the result of this
a signal peptidase -> results in an inactive propeptide
how are propeptides packaged for transport
in large dense core vesicles
what is the significance of POMC
it is a gene that produces a propeptide for melanocyte stimulating hormones, ACTH, beta endorphins, LPH and corticotropin like intermediate peptides
propeptide cleavage is done by what enzyme
synthesizing peptidase
what is the function of catabolic peptidases
cleave active peptides -> inactive
extracellular
catabolic peptidases are usually ______ peptidases while signalling/synthesizing peptidases are ____ peptidases
exo / endo
what is the difference in synthesis between neurotransmitter and neuropeptide
transmitter -> nerve terminal
peptide -> cell body
what is the difference in release between neurotransmitter and neuropeptide
transmitter -> released by synaptic vesicles by exocytosis
peptide -> released from synthetic peptidases by exocytosis
what is the difference in reuptake between neurotransmitter and neuropeptide
transmitter -> recycled at nerve terminal
peptide -> degraded
what is the difference in concentrations between neurotransmitter and neuropeptide
transmitter -> high concentrations at nerve terminal
peptide -> low concentration at nerve terminal
what type of receptors are neuropeptides
G protein coupled
neuropeptide release can ____ or _____ actions of primary neurotransmitters
strengthen or prolong
neuropeptides have five types of functions , what are they
- direct action
- autocrine
- juxtacrine
- paracrine
- endocrine
what does CART stand for
cocaine and amphetamine regulated transcript
what are the 5 types of neuroactive peptides and provide examples if possible
tahcykinin -> substance P
cholecystokinin -> CCK
CART
orexigenic peptides -> neuropeptide Y, ghrelin and orexin
oxytocin and vasopressin
what is one of the earliest neuroactive peptides
tachykinin peptides -> substance P
what is the function of substance P
causes intestinal contraction
tachykinin genes are Gi, Gs or Gq and what is the mechanism for this
Gq
PLC -> IP3and DAG -> Calcium release
true or false - substance P is involved in pain transmission
true
review diagram on slide 5
i
in terms of nociception, substance P is co released with what
glutamatergic sensory afferents
what is another name for pain fibres
C fibres
substance P is in what two types of clinical pain
neuropathic and fibrmyalgia
in terms of Substance P, what reduces the response threshold for noxious stimuli
NK2 and NK3 agonists
what is the active component of chili peppers
capsaicin
capsaicin depletes ______
Substance P
what is the final triggering step of the vomit reflex
substance P release in the CTZ
what is Apripitant
NK1 substance P antagonist used as an anti emetic for chemo and post op nausea
NK1 antagonists have what type of effects in animals
antidepressant effects
what happens when NK1 is knocked out in mice and humans
shows decreased voluntary alcohol consumption in mice and cravings in trials of detoxified alcoholic inpatients
NK2 antagonists have what effects in animals
anxiolytic and antidepressant effects
NK3 antagonists have what effects in humans
antipsychotic effects
what is the function of GI peptide hormones and its mechanism
triggers digestion of fat and protein -> triggers release of digestive enzymes from the pancreas and bile from gallbladder
true or false - CCK peptides act as a hunger stimulant in response to rich foods
false - acts as a hunger suppressant
CCK peptides are designated based on what
length in amino acids
the CCK peptides are thought to act through which nerve
vagus nerve
where are CCK receptors mainly expressed
CNS
polymorphisms of CCK receptors are associated with what problems
panic disorder and schizophrenia
IV administration of CCK4 leads to what
anxiety and panic attacks
CCK receptor antagonists share structure and affinity with what class of drugs
benzodiazepines
chronic benzodiazepine treatment does what to the responsiveness to CCK
decreases neural responsiveness to CCK
during benzodiazepine withdrawal, where is the CCK density upregulated
hippocampus and frontal cortex
proglumide is part of which CCK receptor family ? is it an agonist or antagonist? what is it used for
part of CCKa and CCKb antagonist
-> used to treat stomach ulcers
true or false - CCK receptor antagonists produce anxiolytic effects
true
what is the nocebo effect
expectation of symptom worsening leads to negative outcomes
what is verbally induced nocebo hyperalgesia and what does this result in
increased sensitivity to pain on expectancy -> decreased pain threshold is associated with increased activation of HPA axis -> cortisol release
what kind of treatment reduced hyperalgesia and HPA activity
diazepam treatment
true or false - proglumide, a CCK receptor antagonist, blocked both hyperalgesia and HPA activity
false - only hyperalgesia of verbally induced nocebo
CART alone induced what? CART co adminstration with cocaine does what?
alone -> induces locomotor hyperactivity
co admin -> inhibits motor hyperactivity
CART expression is modified by what?
alcohol, nicotine and opiods
CART is a exo/endogenous psychstimulant
endoCA
true or false - CART is an anorexic peptide
true
where is CART highly expressed
hypothalamus
what is a treatment for binge eating and what does this do to CART expression
rimonabant -> increases CART expression
CART signals what neurotransmitter in suppressing appetite
5HT
true or false - CART stimulates the orexigenic pathways
false - inhibits it
