SUBSTANCE P by RAGHUL PHARMACIST.

SUBSTANCE P by RAGHUL PHARMACIST.

• 1.
  SUBSTANCE P RAGHUL H BPHARMACY(2014-2018) NANDHA COLLEGE OF PHARMACY ERODE TAMILNADU
• 2.
  SUBSTANCE P • Definition •Synthesis • Distribution • Receptors • Mechanism • Functions • Antagonist
• 3.
  Definition • Substance Pis 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.
• 4.
  AMINOACID SEQUENCE OF SUBSTANCEP • Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met
• 5.
  SYNTHESIS • Peptides aresynthesized 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 Pstands 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 receptorTACR1 • 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 Pis the Neurokinin neurotransmitter selectively binds with the NK1 receptor NK1 receptor is have some affinity for other tachykinins
• 9.
  MECHANISM • Substance Pis 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 welldefined 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 Pis a key first responder to most noxious/external stimuli(stressors). • It is an immediate defence,stress,repair,survival system.
• 12.
  FUNCTIONS • Vasodilation • Inflammation •Pain • Mood,anxiety,learning • Vomiting • Cell growth,proliferation,angiogenesis • Migration
• 13.
  FUNCTIONS • VASODILATION • SubstanceP 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: • SubstanceP 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 dueto 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 isassociated with the regulation of mood disorders,anxiety,stress,reinforcement,neuro genesis,respiratory rhythm,neurotoxicity,pain and nociception.
• 17.
  FUNCTIONS VOMITING Vomiting center inthe 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.
• 18.
  FUNCTIONS CELL GROWTH,PROLIFERATION,ANGIOGENE SIS AND MIGRATION: SubstanceP stimulate cell growth in normal and cancer cell line cultures. Substance P promote wound healing of non healing ulcers in humans.
• 19.
  ALL THE BEST THANKYOU