Substance P is an 11-amino acid neuropeptide that acts as a neurotransmitter and neuromodulator. It is widely distributed throughout the nervous system and released from sensory nerve terminals. Substance P binds to neurokinin 1 receptors on cells to trigger various second messenger systems, regulating functions like vasodilation, inflammation, pain, mood, vomiting, and cell growth. Originally discovered in 1931, substance P plays key roles in the body's response to stressors and has clinical significance in conditions involving chronic inflammation, mood disorders, arthritis, cancer, and infections.

1. SUBSTANCE P
Bhagya Siripalli,
Pharmacology, SVIPS

2. Definition
• Substance P is an undecapeptide(a peptide composed of a
chain of 11 amino acid residues) belongs to the tachykinin
family.
• It is a neuropeptide,acting as a neurotransmitter and as a
neuromodulator.
• It is closely related neurokinin A ,produced from a
polyprotein precursor.
• It is widely distributed throughout the nervous sytem of
human and animal species.

3. AMINOACID SEQUENCE OF
SUBSTANCE P
Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met (RPKPQQFFGLM)
with an amidation at the C-terminus.
 Substance P is released from the terminals of specific sensory
nerves. It is found in the brain and spinal cord and is associated
with inflammatory processes and pain.

4. •The original discovery of Substance P (SP) was in 1931
by Ulf von Euler and John H. Gaddum as a tissue extract
that caused intestinal contraction in vitro.
•Its tissue distribution and biologic actions were further
investigated over the following decades.
• The eleven-amino-acid structure of the peptide was
determined by Chang, et. al in 1971.
•In 1983, NKA (previously known as substance K or
neuromedin L) was isolated from porcine spinal cord and
was also found to stimulate intestinal contraction.
DISCOVERY

5. SYNTHESIS
• Peptides are synthesized through translation and
transcription process.
• Substance P is synthesised in the endoplasmic reticulum then
transferred to the Golgi apparatus for packaging and finallly
transported to the cell membrane for exocytic release.
• It is present in high concentration in nerve endings in
selected region of the mammalian brain.

6. DISTRIBUTION
• Substance P stands for Preparation the neurokinin
type 1 receptor is distributed over cytoplasmic and
nuclear membranes of many types of
cells(neurons,glia,endothelia of capillaries and
lymphatics,fibroblasts,stem cells,white blood
cells)and many tissues and organs.
• It excites more cellular processes.

7. RECEPTOR
• Tachykinin receptor TACR1
• Neurokinin 1 receptor NK1R
• Substance P receptor SPR
• It is a G protein coupled receptor found in CNS and
peripheral nervous system.
• Substance P is the Neurokinin neurotransmitter
selectively binds with the NK1 receptor, NK1
receptor is have some affinity for other tachykinins

8. MECHANISM
• Substance P is synthesises by neurons and transported
to synaptic vesicles.
• These are released by the depolarizing action of calcium
dependent mechanisms.
• When NK1 receptor is stimulated,they can generate various
second messengers..which triggers the various effector
mechanism that regulate cellular excitability and function.

9. MECHANISM
The three well defined second messenger system is
stimulation:
1. Via phospholipase C of phosphatidyl inositol,turnover
leading to Calcium mobilization from intra and
extracellular sources.
2. Arachidonic acid mobilization via phospholipase A2
3. cAMP accumulation via stimulation of adenylate
cyclase

10. FUNCTIONS
• Substance P is a key first responder to most
noxious/external stimuli(stressors).
• It is an immediate defence,stress,repair,survival
system.
• Vasodilatation
• Inflammation
• Pain
• Mood, anxiety, learning
• Vomiting
• Cell growth, proliferation, angiogenesis
• Migration

11. FUNCTIONS
VASODILATION
• Substance P is a potent vasodilator.
• It is dependent on nitric oxide release.
• It also has broncho constrictive
properties,administered through the non
adrenergic,non cholinergic nervous system.
PAIN
•It is due to the transmission of pain information into the
central nervous system.
•Substance P coexists with the excitatory
neurotransmitter glutamate in primary afferents that
respond to pain stimulation

12. FUNCTIONS
INFLAMMATION:
• Substance P and other sensory neuropeptides can be
released from the peripheral terminals of sensory nerve
fibers in the skin,muscle and joints.
• This release is involved in neurogenic inflammation which
is a local inflammmatory response to certain types of
infection or injury.
MOOD,ANXIETY,LEARNING
•Substance P is associated with the regulation of mood
disorders, anxiety, stress, reinforcement, neuro genesis,
respiratory rhythm, neurotoxicity, pain and nociception.

13. FUNCTIONS
VOMITING
•Vomiting center in the medulla called the area postrema, contains
high concentrations of substance P and its receptors with other
neurotransmitters such as choline, histamine, dopamine, serotonin
and opioids.
•Their activation stimulates the vomiting reflex.
CELL GROWTH,PROLIFERATION,ANGIOGENE SIS AND MIGRATION:
Substance P stimulate cell growth in normal and cancer cell line
cultures.
Substance P promote wound healing of non healing ulcers in
humans.

14. Quantification in disease
Blockade for diseases with a chronic immunological
component
Dermatological disorders: eczema/psoriasis, chronic
pruritus: High levels of BDNF and substance P have been
found associated with increased itching in eczema.
Mood disorders, major depressive disorder, anxiety
disorders
Arthritis, Cancer,
Infections: HIV-AIDS, Measles, RSV, others, Inflammatory
bowel disease (IBD)/cystitis
Other findings like Denervation super sensitivity, Male
aggression
CLINICAL SIGNIFICANCE

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