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NEUROPEP
TIDES
SUMIT KUMAR
Research Scholar
Integral University Lucknow
Neuropeptides
 Neuropeptides are small protein like molecules (peptides)
used by neurons to communicate with each other.
(Autocrine/paracrine).
 Neuronal signaling molecules(not recycled back into the
cell once secreted, unlike glutamate, dopamine, serotonin
etc.)
 Responsible for brain function:
• Analgesia.
• Food intake
• Learning & memory.
• Metabolism, reproduction.
• Social behaviors .
Eg: Neuropeptide Y(NPY), Cholecystokinin(CCK),
Tachykinins(substance P, Neurokinin), Arginine
Vasopressin(AVP), Corticotropin releasing factor(CRF)
Neuropeptide Y
( NPY )
Neuropeptide Y(NPY)
• 36-amino acid .
• Acts as a neurotransmitter in the brain & ANS.
BRAIN-NPY ANS -NPY
Produced mainly by hypothalamus. Produced mainly by neurons of
the sympathetic nervous system
food intake. Strong Vasoconstrictor
storage of energy as fat. Growth of fat tissue
anxiety and stress, voluntary
alcohol intake, blood pressure, pain
perception.
Affecting the circadian rhythm
Controlling epileptic seizures
NPY RECEPTORS
• G-protein coupled Receptors (GPCR)
• 5 Types : Y1-Y5in mammals - 4 in humans
 Y1-NPY1R & Y5-NPY5R : feeding stimulator
(appetizer).
 Y2-NPY2R & Y4-NPY4R : appetite inhibition
(anorectic)
• Activated neuropeptide receptors release the Gᵢ
subunit from the heterotrimeric G protein complex.
This Gᵢ subunit in turn inhibits the production of the
second messenger cAMP from ATP.
• Therapeutic targets for obesity.
Tachykinin
( TAC )
Tachykinin (TAC)
• Largest families of neuropeptides.
• Characteristic:
C-terminal sequence
“Phe-X-Gly-Leu-Met-NH2”
where X is either an Aromatic or an Aliphatic amino acid.
Preprotachykinin Protachykinin Tachykinin
(PPTAC) (PTAC) (TAC)
----
TAC -1
gene
Neurokinin A
Neurokinin k (neuropeptide K)
Neuropeptide γ
Substance P(SP)
TAC-3
gene
Neurokinin B
Table: List of different Tachykinin produced by Human tachykinin genes
Tachykinin receptors (GPCR)
NK1R
NK2R NK3R
Agonist- Substance P Neurokinin A Neurokinin B
Antagonist-
Aprepitant, casopitant,
Fosaprepitant, Maropitant Antiemetic drugs
(treatment of chemotherapy induced
delayed nausea/emesis)
Activated TAC receptors release the Gq subunit from
the heterotrimeric G protein complex. This Gq subunit
in turn leads to activation of phospholipase C & hence
formation of phosphoinisitol triphosphate.
Substance P(SP)
 Belongs to the tachykinin(TAC) neuropeptide family.
 Undecapeptide- a peptide composed of a chain of 11 amino acid
residues
Receptors- NK1R- GPCR
Amino acid residues that are responsible for the binding of SP and
its antagonists are present in the extracellular loops and transmembrane
regions of NK1.
SP antagonist (SPA)-Capsaicin is clinically used as an analgesic and an
antiinflammatory agent to reduce pain associated with arthritis and many
types of neuralgia(Capsaicin has been shown to reduce the levels of
substance P).
SPA – Aprepitant used as antiemetic drug in treatment of chemotherapy
induced delayed vomiting.
Substance P could promote wound healing of nonhealing ulcers in
humans.
Substance P as a potent vasodilator. Substance P induced vasodilatation
is dependent on nitric oxide release.
Neurokinin A (Substance K)
Member of the tachykinin family .
Neurokinin A binds to the GPCR(NK2R) Causing
the release of inositol phosphate and calcium second
messengers(Secondary messenger).
Therapeutic role:
Concentrations of neurokinin A is an independent
indicator of poor prognosis in certain cancers such as
carcinoids. (Higher circulating neurokinin A- poor
cancer prognosis)
NKA Antagonist (MEN 11420)used in asthma for
suppression of bronchial constriction.
Arginine Vasopressin
(AVP)
Arginine Vasopressin (AVP)
Antidiuretic hormone (ADH)
Peptide hormone-nonapeptide , M.Wt 1,099
Synthesized in the paraventricular and supraoptic nuclei of
the hypothalamus
Stored in posterior pituitary gland .
Vasoconstrictor
Water excretion
AVP may also be released directly into the brain.
Role in social behavior
Sexual motivation
Maternal responses to stress
AVP Receptors (GPCR)-V1a, V1b, V2.
Neuropeptides

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Neuropeptides

  • 2. Neuropeptides  Neuropeptides are small protein like molecules (peptides) used by neurons to communicate with each other. (Autocrine/paracrine).  Neuronal signaling molecules(not recycled back into the cell once secreted, unlike glutamate, dopamine, serotonin etc.)  Responsible for brain function: • Analgesia. • Food intake • Learning & memory. • Metabolism, reproduction. • Social behaviors . Eg: Neuropeptide Y(NPY), Cholecystokinin(CCK), Tachykinins(substance P, Neurokinin), Arginine Vasopressin(AVP), Corticotropin releasing factor(CRF)
  • 4. Neuropeptide Y(NPY) • 36-amino acid . • Acts as a neurotransmitter in the brain & ANS. BRAIN-NPY ANS -NPY Produced mainly by hypothalamus. Produced mainly by neurons of the sympathetic nervous system food intake. Strong Vasoconstrictor storage of energy as fat. Growth of fat tissue anxiety and stress, voluntary alcohol intake, blood pressure, pain perception. Affecting the circadian rhythm Controlling epileptic seizures
  • 5. NPY RECEPTORS • G-protein coupled Receptors (GPCR) • 5 Types : Y1-Y5in mammals - 4 in humans  Y1-NPY1R & Y5-NPY5R : feeding stimulator (appetizer).  Y2-NPY2R & Y4-NPY4R : appetite inhibition (anorectic) • Activated neuropeptide receptors release the Gᵢ subunit from the heterotrimeric G protein complex. This Gᵢ subunit in turn inhibits the production of the second messenger cAMP from ATP. • Therapeutic targets for obesity.
  • 7. Tachykinin (TAC) • Largest families of neuropeptides. • Characteristic: C-terminal sequence “Phe-X-Gly-Leu-Met-NH2” where X is either an Aromatic or an Aliphatic amino acid. Preprotachykinin Protachykinin Tachykinin (PPTAC) (PTAC) (TAC)
  • 8. ---- TAC -1 gene Neurokinin A Neurokinin k (neuropeptide K) Neuropeptide γ Substance P(SP) TAC-3 gene Neurokinin B Table: List of different Tachykinin produced by Human tachykinin genes
  • 9. Tachykinin receptors (GPCR) NK1R NK2R NK3R Agonist- Substance P Neurokinin A Neurokinin B Antagonist- Aprepitant, casopitant, Fosaprepitant, Maropitant Antiemetic drugs (treatment of chemotherapy induced delayed nausea/emesis) Activated TAC receptors release the Gq subunit from the heterotrimeric G protein complex. This Gq subunit in turn leads to activation of phospholipase C & hence formation of phosphoinisitol triphosphate.
  • 10. Substance P(SP)  Belongs to the tachykinin(TAC) neuropeptide family.  Undecapeptide- a peptide composed of a chain of 11 amino acid residues Receptors- NK1R- GPCR Amino acid residues that are responsible for the binding of SP and its antagonists are present in the extracellular loops and transmembrane regions of NK1. SP antagonist (SPA)-Capsaicin is clinically used as an analgesic and an antiinflammatory agent to reduce pain associated with arthritis and many types of neuralgia(Capsaicin has been shown to reduce the levels of substance P). SPA – Aprepitant used as antiemetic drug in treatment of chemotherapy induced delayed vomiting. Substance P could promote wound healing of nonhealing ulcers in humans. Substance P as a potent vasodilator. Substance P induced vasodilatation is dependent on nitric oxide release.
  • 11. Neurokinin A (Substance K) Member of the tachykinin family . Neurokinin A binds to the GPCR(NK2R) Causing the release of inositol phosphate and calcium second messengers(Secondary messenger). Therapeutic role: Concentrations of neurokinin A is an independent indicator of poor prognosis in certain cancers such as carcinoids. (Higher circulating neurokinin A- poor cancer prognosis) NKA Antagonist (MEN 11420)used in asthma for suppression of bronchial constriction.
  • 13. Arginine Vasopressin (AVP) Antidiuretic hormone (ADH) Peptide hormone-nonapeptide , M.Wt 1,099 Synthesized in the paraventricular and supraoptic nuclei of the hypothalamus Stored in posterior pituitary gland . Vasoconstrictor Water excretion AVP may also be released directly into the brain. Role in social behavior Sexual motivation Maternal responses to stress AVP Receptors (GPCR)-V1a, V1b, V2.