Neuropeptides Flashcards
Describe the structure of neuropeptides ?
Chains of 2 or more amino acids
The adjacent amino acids are joined by peptide bonds
Usually 3-36 amino acids long
What are the different families of neuropeptides ?
Opioid peptides - for endogenous pain Gut-brain peptides Hypothalamic - releasing hormones which affect other tissues Pituitary hormones Miscellaneous peptides
What is the benefit of neuropeptides including the sequences of other neuropeptides ?
It means there is a large variety of neuropeptides to be made
Eg beta-endorphin contains both alpha endorphin and methionine enkephalin
How are neuropeptides synthesised ?
Come from a large precursor protein made in rER called a prepropeptide
At the rER the signal that tells the cell to secrete the peptide is removed creating a propeptide which goes to the Golgi apparatus
And is packaged into asynaptic vesicle
In the synaptic vesicle the propeptide is cleaved into active peptide by peptide see
Vesicles are then transported to the axon terminal via micro tubules and by fast axonal transport
What is another name for synaptic vesicles containing neuropeptides ?
Large dense core vesicles - 90-250nm
Present in reserve pool of axon terminal
What happens to neuropeptides after there release !?
They are destroyed by peptidase so - not recycled
What factor helps to increase the diversity of neuropeptides ?
They are produced by genes which express an mRNA strand to the produce the peptide however the mRNA strand can be spliced differently allowing many different neuropeptides to be produced
What enzyme converts the prepropeptide into the propeptide ?
Signal peptidase - it clips the prepropeptide tail
What effect does cleaving the propeptide in the vesicle have ?
It means when it is cleaved there could be more than 1 active peptide in the vesicle
- these peptides could enhance each other’s effects or they could oppose one another’s effects
What is the difference about the release of small molecule neurotransmitters and neuropeptides ?
Neuropeptides are stored in the reserve pool so they are further back so a larger frequency action potential is required to produce a larger influx of calcium ions to cause the release of neuropeptides
What does it mean by some neuropeptides can be released extrasynaptically ?
Means that so,e neuropeptides can be released from the cell body - induced by calcium ions
Eg is the release of substance P in dorsally root ganglion cells
When small molecule neurotransmitters and peptides are colocalised what are the actions caused by the. ?
They can either be complimentary to one another or they may have completely different effects
What are some examples of colocalisation ?
CCK with dopamine in Mesolimbic and mesocortical pathways
Galanin with acetylcholine in basal forebrain
Enkephalins/substance P with GABA in basal ganglia
Substance P with serotonin in medulla
VIP with acetylcholine in submandibular gland
What are the 3 modes in which peptides are expressed in neurons ?
1- present at high levels under normal conditions - substance P
2- normally expressed at low levels and unregulated as necessary by a stimulus - galanin, neuropeptide y
3- expressed early during development and then down regulated postnatally- somatostatin
When are peptides referred to as neuromodulators?
When a neuropeptide is released alongside a small molecule NT and it interacts with the classical NT but has no effect of its own
Define: neuromodulator
Substance that modulates the action of neurotransmitters rather than having a direct physiological response of its own
What are neurohormones ?
Act as either a classical hormone or locally as a neurotransmitter or neuromodulator
- produced by neurones or other cells
They have more wide spread effects compared to neuropeptides
What is the pituitary gland ?
“Master gland”
Has an anterior and posterior parts which secrete hormones which influence cells and basically all physiological functions
What controls the release of hormones from the pituitary gland ?
Hypothalamus
Neurosecretory neurons from the hypothalamus control release from anterior - the hormones released from hypothalamus are releasing ones or inhibiting ones
What is vasopressin ?
9 aa peptide
Synthesis of precursors occurs in paraventricular and suproptic nuclei of hypothalamus
Released in the posterior pituitary gland and also in forebrain, spinal cord and BRAINSTEM nuclei
Has 3 VP receptors - GPCRs
What are the physiological roles of vasopressin ?
Regulation of fluid balance and electrolyte balance
Regulation of blood pressure - vasoconstrictor
Activates hypothalamus - pituitary- adrenocortical system during stress
What is neuropeptide y ?
36 aa peptide distributed in CNS and PNS
Have neurosecretory and cardiovascular functions
At least 5 classes of receptors
Involved in promoting appetite - especially carbs
What are tachykinins?
Broad family - substance P, neurokinin A, neurokinin B and neuropeptide K
Apart from B they all come from alternative splicing of pre-protachykinin
What are the receptors and affinities of tachykinin ?
NK- 1,2,3
1- SP> NKA > NPK> NKB
2- NPK> NKA> NKB> SP
3- NKB> NKA > SP
What is substance P ?
Neuropeptide which has a major function at sensory receptors in PNS
Involved in transmission of somatosensory info mainly pain and inflammation
When release at site of injury it sensitises the area
What are opioids involved in ?
Controlling pain, immune responses and other body functions
They lessen pain and produce euphoria
Give examples of endogenous opioids
Dynorphins Peptide E and F Alpha, beta and gamma endorphin Leu- enkephalin Met- enkephalin
What are the 3 propeptide that endogenous peptides are produced from ?
Proenkephalin
Proopiomelanocortin
Prodynorphin
