Substance p

Substance P description

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. D ISCOVERY

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. REC E PTOR 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. MECHANI SM The three well defined second messenger system is stimulation: Via phospholipase C of phosphatidyl inositol,turnover leading to Calcium mobilization from intra and extracellular sources. Arachidonic acid mobilization via phospholipase A2 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. FUNCT I ONS 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. FUNCT I ONS 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. FUNCT I ONS 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 C LINICAL SIGNIFICANCE

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