Purinergic receptor 1

different types of purinergic receptors and their phsiological role in human body

1. PURINERGIC RECEPTOR PRESENTED BY Sandhya Talla M.PHARM (FIRST YEAR) DEPARTMENT OF PHARMACOLOGY 11/08/2016 1

2. CONTENT History & Introduction ATP as neurotransmitter Synthesis, store, release and metabolism of ATP Types of purinergic receptor Distribution of purinergic receptors Structure of purinergic receptor Purinergic signalling Role of purinergic receptor Therapeutic potential Recent trends 2

3. 3 The transmitter substance release from Non-cholinergic & Non- adrenergic nerves of Gut may be ATP or some related purine nucleotide. These nerves has been termed as “Purinergic nerves” Geoffrey Burnstock(1972) (Molecular M.N.,2008) HISTORY (Ghosh,2008)

4. INTRODUCTION What is purinergic receptors? The purinergic system involves the purine nucleotides, ATP , ADP, and the nucleoside, adenosine Purinergic nerves are located on Aurbach’s plexus. 4

5. 5 Aurbach’s plexus is a collection of nerve fibre and that are mainly found in the muscle tissue of human intestine . These plexus are mainly responsible for generating peristalsis movement. AURBACH’S PLEXUS:-

6. The substance must be released from terminal axon when nerves are activated. ATP is contained in synaptic vesicles of both adrenergic and cholinergic neurons, and it works as an energy currency. ATP is released on nerve stimulation in a Ca 2+ -dependent fashion 6 ATP as a Neurotransmitter ( burnstock,2006 )

7. 7 ATP ADP AMP Adenosine Inosine ATpase Adenosine deaminase Adenosine uptake P2 purinoreceptor Adenosine Large opaque vesicle Containing ATP SMOOTH MUSCLE Synthesis , store ge, release and metabolism of ATP ( burnstock,2014)

8. . 8 P1 P2 A1 A2 A3 P2X P2Y Purinergic receptor Types of Purinergic Receptors (Burnstock et al ,2012 ) P2Y1,P2Y2,P2Y4,P2Y6 P2X1,P2X2,P2X3,P2X4

9. Receptors Main distribution A1 Brain, spinal cord,testis,heart. A2 Brain, Heart,spleen, lungs. A3 Lung,Liver, Brain, Testis. 11/08/2016 9 Receptors Main distribution P2X1 Smooth muscle, cerebellum, platelets P2X2 Smooth muscle, sensory, gangalia P2X3 Sympathetic neurons P2X4 CNS, testis,colon Receptors Main distribution P2 Y1 Epithelial cell,Endothelial cell, P2Y2 Immun cell, osteoblast,kidney tubules P2Y4 Endothelial cell P2Y6 Placenta,T cell,thymus Distribution of purinergic receptors (Burnstock et al, 2012)

10. P1 receptor :- (G- protien couple receptors) 7-Transmembrane(TM) domains of hydrophobic amino acid---constitute an α -helix of ~21–28 amino acids 10 Structure of Purine Receptor (Burnstock et.,al 2012)

11. P2x receptor :- ( Ligand gated ion channel) Large extracellular loop, with 10 conserved cysteine residues forming a series of disulfide bridges. 11 Structure of Purine Receptor

12. P2y receptor :-( G- protien couple receptor) Some TM-spanning regions, particularly TM3, TM6 & TM7 and structural diversity of intracellular NH2 & COOH terminus among P2Y sub-Types 12 Structure of Purine Receptor

13. Short term neuronal signalling - secretion vasodilation Co-transmission Long term neuronal signalling Cell proliferation Cell differentiation Inflammation 13 Purinergic Signalling (Burnstock,2014 l)

14. 14 Co-transmission (Burnstock,2014)

15. 15 Cell proliferation and differentiation (Burnstock, 2014)

16. In Central Nervous System In Respiratory System In Cardiovascular System In Gastrointestinal Tract In endocrine system In Urinary system 16 Role of purinergic receptor

17. Release of excitatory neurotransmitter (GABA,glycine) Release of inhibitory neurotransmitter (glutamate) Anticonvulsant effects 17 Central nervous System (Burnstock,2008)

18. Purine increases mucus secretion from goblets cells. Purinergic activation causes bronchoconstriction. 18 Respiratory system

19. 19 Cardiac system (Burnstock,2003)

20. Slows AV nodal conduction (negative dromotropy) Decrease heart rate (negative chronotrophy) Decrease atrial contractality (negative contraction) Inhibits pacemaker 20 It causes

21. Relaxation of stomach. Decreases peristalsis movement. P2x 3 receptor present on gut wall produces pain sensation 21 Gastrointestinal Tract (Fernando, et al 2014)

22. Purinergic signaling causes contraction of urinary bladder. Purinoceptor involved in regulation of renin secretion, glomerular filtration and transport of water, ions, nutrients. P2x 3 responsible for micturation reflux and pain 22 Urinary System

23. ATP stimulate release of insulin ATP modulate aldosterone production ATP inhibit secretion of estradiol and progesterone from ovary Inhibit lipolysis 23 Endocrine Glands

24. 1) Parkinson’s disease :- Adenosine A2a receptor antagonists are mainly used. 2) Epilepsy :- Adenosine by activation of A1 receptors in hippocampus exerts predominant inhibitory effects. These inhibitory actions of adenosine can be used therapeutically to suppress seizures. 24 Therapeutic Potential ( Burnstock,et al 2003)

25. 3) Ischaemia :- Adenosine used as a cytoprotective agent during myocardial ischaemia i) improved tissue perfusion ii) anti-inflammatory action 25 Therapeutic Potential (Burnstock, et,al 2003)

26. Atherosclerosis:- Adenosine and ATP have a number of cardiovascular protective effect in addition of vasodilation ,including promotion of the endothelial and smooth muscle cell proliferation and increased in the expression of vascular endothelial grawth factor (VEGF). 26 Therapeutic Potential (Burnstock,2003)

27. Purinergic signalling in ovary Acupuncture : a Novel hypothesis for involvment of purinergic signalling 27 Recent Trends

28. ATP produced inside the cell can be released into the extracellular area in different ways. purinergic activity in ovary – including sensitivity of gonadotropin in several ovarian cells types, i.e Granulosa cell , theca cell. role of ATP as an important intraovarian messenger and regulate the ovarian function. 28 Purinergic signalling in ovary (Molecular Reproduction and development,2015)

29. 29 Purinergic signalling in ovary

30. 30 Acupuncture: A novel hypothesis for the involvement of purinergic signalling ( Burnstock,2009)

31. 31 References Molecular inervention ,M.N Ghosh; purinergic Nerves, 2004 M.N Ghosh purinergic receptors fundamental of experiments Annualreviews;structural and chemical organisation of Aurbach plexus. Geoffrey Burnstock (2006);Historical review: ATP as a neurotransmitter Geoffrey burnstock (2006 ); historical review : ATP as a neurotransmitter Geoffrey Burnstock (2012) purinergic signaling in healthy and diseased skin ;volume 132 Geoffrey Burnstock (2012);purinergic signaling in healthy and diseased skin Geoffrey Burnstock (2012);purinergic signaling in healthy and diseased skin Geoffrey Burnstock (2014);purinergic signaling;from discovery to current development Geoffrey Burnstock (2014);purinergic signaling ;from discovery to current development Geoffrey Burnstock (2008) ;purinergic signaling and disorder of CNS Geoffrey burnstock 2003;involvment of purinergic signaling in cardiovascular diseased fernando.ochoa-corts (2014) potential for developing purinergic drug for GIT disesead Geoffrey Burnstock;(2008) ;purinergic signaling and disorder of CNS Geoffrey Burnstock (2003); Involvment of purinergic signaling in cardiovascular diseased Angelica s (2015);purinergic signaling In overy molecular Reproduction and development Geoffrey Burnstock (2009)Acupuncture: A novel hypothesis for the involment purinergic signaling

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