Neuropeptides & other NTs

unlike other NTs, neuropeptides normally contain ________ amino acids

3-36

do neurons that produce neuropeptides tend to be long or short?

short

neuropeptides are created as biologically inactive precursors in the _____

ER

neuropeptides are packaged into __________ for release

large dense-core vesicles

• dock further away from synapse

when mRNA are translated on ribosomes in the ER, the product is called:

pre-propeptides

pre-propeptides contain a _________ sequence needed to get internalized into secretory vesicles which bud off at the golgi

N-terminus signal

what happens to the N-terminus signal sequence once the pre-propeptide has been internalized into secretory vesicles that bud off to the golgi?

the signal sequence is cleaved off

what happens to the propeptide in the golgi?

it is cleaved to find the active form of the peptide

is a propeptide active or inactive?

inactive/nonfunctional

depending on the tissue, different peptides are created by the same propeptide due to…

• differential splicing

• mRNAs

• different pposttranslational processing

can different neuropeptides be found in the same large dense core vesicles?

yes

do neuropeptides have a mechanism of rapid clearnace from the ECF?

no

how are neuropeptides broken down?

endopeptideases and exopeptidases found on extracellular membranes throughout the body

can neuropeptides act over long distances?

yes

high frequency/bursting stimulation leads to what kind of synaptic release?

extra synaptic

normal firing stimulation leads to what type of release?

synaptic releae

opiod system

Play important roles in physiologic functions

• pain relief (analgesia)

• euphoria induction

• stress resilience

• cardiovascular protection

• food intake control

• More

Act through multiple receptors throughout the body

opiod peptides include…

1. endorphins

2. enkephalins

3. dynorphins

what type of receptors do opiods activate?

G protein-coupled

most peptide recpetors are…

7-TM G-protein coupled receptors

describe affinity of G-protein coupled receptors for neuropeptides

greater affinity (since NT is often released far away)

opiod G protein coupled receptors are negatively coupled to ___________

adenyl cyclase

beta and gamma subunits off of opiod receptors affect…

K+ and Ca2+ channels

4 different receptor types acted on by opiates

1. mu

2. delta

3. kappa

4. sigma

which opiod receptor subtype is involved in euphoria and addiction?

mu

what makes opiod addiction hard to treat?

unique combination of receptor subunits impacts signaling pathways that are activated - widespread effects

where can opiod receptors be found?

pre and post-synaptically

role of mu opiod receptor

alters VTA signaling → net excitatory or inhibitory effect as part of the reward pathway

corticotrophic releasing hormone/factor (CRH)

• Significant component of the HPA axis which regulates the stress response

• Synthesized in the PVN (paraventricular nucleus) in hypothalamus

• Triggers the release of adrenocorticotrophic hormone (ACTH) from pituitary (along with vasopressin)

• Released into portal circulation (mechanism by which pituitary is activated

• Also released synaptically into brainstem, cerebral cortex, amygdala and bed nucleus of the stria terminalis

which NT is a significant component of the HPA axis and stress resposne?

CRH

where is CRH synthesized?

hypothalamus (paraventricular nucleus)

CRH triggers the release of ACTH (adrenocorticotrophic hormone) from __________

pituitary

describe localization of corticotrophin hormone receptor type 1

widespread localization in the brain

describe localization of corticotrophin hormone receptor type 2

localized to lateral septal nuclei of the forebrain

• activated by urocortin

what 2 NTs are synthesized in the hypothalamus and released into the blood stream?

1. vasopressin

2. oxytocin

vasopressin regulates…

water reabsorption

oxytocin stimulates…

• uterine contraction (labor)

• milk let down (lactation)

vasopressin has ____ receptors (Gq)

3

oxytocin has ___ receptors (Gq)

1

neurotensin system may regulate …

doamine system

neurotensin system is involved in…

• reward

• energy balance

neurotensin regulates communication between what 2 structures?

1. VTA

2. nucleus accumbens

what NT is involved in the sleep/wake cycle and other motivational behaviors?

orexins (hypocretins)

what NT is important in regulating feeding behavior

neuropeptide Y

purinergic system

ATP, ADP, and adenosine link homeostatic mechanisms with neuromodulation

purinergic system

broadly expressed in brain where it modulates other NT systems

adenosine receptors are key modulators of _______

sleep

site of action of caffeine

adenosine receptors

endocannabinoid system roles

•appetite and digestion

•sleep

•Pain sensation

•inflammation and other immune responses

•mood

•metabolism

•learning and memory

•reproduction system function