3. 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.
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.
8. RECEPTOR
• Substance P is the Neurokinin
neurotransmitter selectively binds with the
NK1 receptor
NK1 receptor is have some affinity for other
tachykinins
9. 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.
10. 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
11. FUNCTIONS
• Substance P is a key first responder to most
noxious/external stimuli(stressors).
• It is an immediate defence,stress,repair,survival
system.
13. 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.
14. 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
15. FUNCTIONS
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
affarents that respond to pain stimulation.
16. FUNCTIONS
MOOD,ANXIETY,LEARNING
Substance P is associated with the
regulation of mood
disorders,anxiety,stress,reinforcement,neuro
genesis,respiratory
rhythm,neurotoxicity,pain and nociception.
17. 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 activationn stimulates the vomiting
reflex.