research scholar

1. Presentation on
Purinergic receptor
Presented by: Presented to:
Rabiya Ahsan Dr. Anuradha Mishra
(Research scholar) (Associate Professor Jr.)
faculty of pharmacy integral university
Integral University Lucknow
2020-2021
1

2. Introduction
Purinergic receptor
• Purinergic receptors, also known as purinoceptors, are a family of
plasma membrane molecules that are found in almost all mammalian
tissues. Within the field of purinergic signalling, these receptors have
been implicated in learning memory, locomotor and feeding behavior,
and sleep.
• The Purinergic receptor system involves nucleotides, ATP, ADP and
the nucleosides, adenosine.

3. • Purinergic signalling is a form of extracellular signalling mediated by
purine nucleotides and nucleosides such as adenosine and ATP.
• Extracellular pyrimidines (Uridine, UDP, UTP)
Fucntion of Adenosine
• It act as a neuromodulator
• Cellular energy transfer
• Ischemic preconditioning

4. Classification
PURINE
RECEPTOR
P2
P2X
P2Y
P1 (Adenosine)
A1
A2
A2A
A2B
A3

5. Adenosine
• Adenosine is naturally occurring endogenous purine nucleoside.
• Adenosine is made up of adenine attached to a ribose.
Physiological and pharmacological role of Adenosine
• In the body, adenosine helps in cellular energy transfer by forming
molecules like adenosine triphosphate (ATP) and adenosine
diphosphate (ADP).
• Adenosine also plays a role in signalling various pathways and
functions in the body by forming signally molecules like cyclic
adenosine monophosphate (cAMP).

6. Metabolism of ATP.
ATP
ADP
AMP
Adenosine
Inosine
• It is released by nearly all cells and is generated in the extracellular space.
• Adenosine is extracellularly signalling agent within the CNS and PNS.
ATpase/
-PO4
-PO4
-PO4/adenosine kinase 5’neucleotidase

7. Mechanism of adenosine

8. Role of purinergic receptor
A1 Cardiovascular • Slow AV nodal conduction
• Decreased heart rate
• Decreased atrial contractility
• Decreased B-adrenergic tone
Renal • Inhibits release of renin
• Increased reabsorption of sodium in PCT
• Vasocontriction of afferent arteriole and decreased GFR
CNS • Decreased neurotransmitter release
• Sedation
• Anticonvulsant effects
Metabolic • Inhibits lipolysis
• Increased insulin sensitivity
A2A Cardiovascular • Coronary and peripheral vasodilation
• Inhibit platelets aggregation
A2B Pulmonary • Vasodilation
A3 Pulmonary Mast cell release of allergic mediators

9. A1 receptors
A1 receptor are present in smooth muscles throughout the vascular system
• Effector mechanism:
 Inhibition of cAMP
Increased K+ permeability
Inhibition of Ca2+ channels
Activation of phospholipase C
• Agonist: N6-Cyclopentyladenosine, N(6)-cyclohexyladenosine
• Antagonist: Non-specific: Caffeine, Theophylline
• Specific: Bamifylline, Rolofylline

10. A2A receptors
• Distribution: Brain, Heart, Blood.
• Superclass: GPCR – Gs
• Effector mechanisms:
Activates adenylate cyclase → ↑ cAMP
Activates phospholipases C → ↓Intracellular Ca levels
• Agonist: Regadenoson, Limonene
• Antagonist: Preladenant, Istradefylline, Vipadenant

11. A2B receptors
• Distribution: GIT, GUT, lungs
• Superclass: GPCR – Gs
• Effector mechanisms:
Activates adenylate cyclase → ↑ cAMP
↑Intracellular Ca levels.
Agonist: N-ethylcarboxamido adenosine,

12. A3 receptors
• Distribution: Kidney, testis, mast cells, eosinophills
• Superclass: GPCR – Gi/Gq
Effector mechanisms:
• Inhibits adenylate cyclase → cAMP
• Activates phospholipases C&D
• Influx of Ca & release from stores
Agonist: N methyl adenosine, Inosine
Antagonist: Theophylline

13. Therapeutics intervention
Respiratory system
Bronchial asthma:
• Adenosine receptor antagonist-theophylline
• selective A1 receptor antagonist- bamiphylline.
Mechanism-Pulmonary vasodilation by A2 receptors,
• Increase AMP-vascular smooth muscle relaxation
• Stimulation of K+ ATPase channel

14. CNS
Epilepsy:
Adenosine-inhibitory modulator of brain activity , activation of A1
receptors
Adenosine kinase- major metabolic enzyme predominantly expressed
in adult brain .
Parkinsons disease:
A2a receptor antagonist:- Istradefylline

15. CVS
Ischaemia/reperfusion injury:
Ischaemic preconditioning(IPC)
Adenosine
• Adenosine receptor stimulation reduces myocardial damage following
ischaemia Adenosine reduces ischaemia by-
Improved tissue perfusion
Anti inflammatory action
Direct intracellular effect
Hypolipidemic agent:
• Elevated TG levels-independent risk factor of CAD

16. Platelet:
Platelets are rich in A2A receptors
• Adenosine -> increases cAMP -> decreased platelet aggregation.
• Dipyridamole inhibits adenosine reuptake ,decreased platelet
aggregation, vasodilation.

17. P2Y receptors
• P2Y receptors are a family of purinergic G protein-coupled receptors,
stimulated by nucleotides such as ATP, ADP, UTP, UDP and UDP-
glucose.
• P2Y receptors have been cloned in humans: P2Y1, P2Y2, P2Y4, P2Y6,
P2Y11, P2Y12, P2Y13 and P2Y14.
• P2Y receptors are present in almost all human tissues where they
exert various biological functions based on their G-protein coupling.
• P2Y receptors mediate responses including vasodilation, blood
clotting,[ and immune response.

18. Pharmacology of P2y receptors
• Many commonly prescribed medications target P2Y receptors, and active
research is being conducted into developing new drugs targeting these
receptors.
• The most commonly prescribed drug targeting P2Y receptors is
clopidogrel, an antiplatelet medication which acts on the P2Y12 receptor
in a manner shared with other thienopyridines.
• Other pharmaceutical applications include denufosol, which targets P2Y2
and is being investigated for the treatment of cystic fibrosis, and
diquafosol, a P2Y2 agonist used in the treatment of dry eye disease.

19. • P2Y6 receptors have been shown to play a role in cerebral
vasodilation. UDP-analogs (CCL+MRS2578) which bind to this
receptor have been investigated as possible treatments for migraines.
• P2Y11 is a regulator of immune response, and a common
polymorphism carried by almost 20% of North European caucasians
give increased risk of myocardial infarction, making P2Y11 an
interesting drug target candidate for treatment of myocardial
infarction.
• In addition to established uses, pharmaceutical research has been
conducted into the role of P2Y receptors in osteoporosis, diabetes,
and cardio-protection.

20. Reference
• www.sciencedirect.com/topics/nursing-and-health-
professions/adenosine
• "Purinergic (P2Y) Receptors". Tocris Bioscience. Retrieved 2020-11-12.
• Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL,
Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman
GA (September 2006). "International Union of Pharmacology LVIII:
update on the P2Y G protein-coupled nucleotide receptors: from
molecular mechanisms and pathophysiology to therapy"

21. Thank you