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Receptors
Presented by
Kamlesh V. Warokar
M.Pharm
( Dept. of Pharmacology)
03-03-2017 1
• Introduction
• Adenosine Receptors
• Drugs
• Therapeutic Role of AR
• Key References
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Introduction:
• Adenosine is naturally occurring endogenous purine
nucleoside.
attached to a ribose.
• t ½ : 10 sec.
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• Metabolite of ATP.
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• It act as a neuromodulator
• Ischemic preconditioning
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Adenosine Receptor
(AR)
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• Purinergic G-protein coupled receptor.
A1
A2A
P1 (Adenosine) A2
A2B
Purinergic A3
receptors
P2X
P2
P2Y
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• There are four types of AR.
• Each receptors are encoded by a separate gene and has
different function.
• ARs are widely distributed throughout the body basically
all cells.
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• It is Hepthahelical G-Protein
coupled receptors.
- A2A-AR (412),
- A3-AR (318).
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• A1 receptor is most conserved AR sub-type among
species.
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Brain,
Eye, Skeletal Muscle, Liver, Kidney,
Adrenal
Gland, Adipose Tissue, Salivary Glands,
Atria
Esophagus, Colon, Testis, Lung
(Bronchi),
Antrum Pancreas
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Gi
• A1
cAMP K+
Go
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CNS:
• Decrease neurotransmitter release
• Sedation
CVS:
• -ve chronotropy
• -ve inotropy
• -ve dromotropy
• Inhibit L-type Ca+ channels
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RENAL:
• Inhibits renin release
• Vasoconstriction of afferent arteriole
METABOLIC:
• Inhibits lipolysis
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• It act as a neuromodulators.
A2-AR
A2A-AR A2B-AR
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• Having high agonist affinity.
Spleen,
Thymus,
Leukocyte,
Blood Other
Heart, Lung, Blood brain
Platelets,
Tuberculum, Vessels regions
Olfactory
Bulb
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GS
olf
A2A-AR cAMP
Golf
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CNS:
• Modulate neurotransmission of GABA, Glutamate
CVS:
• Coronary and peripheral vasodilation
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• Low agonist affinity.
Cecum, A.T,
Colon, Lung, Blood Vessels, Brain,
Bladder Kidney,
Eye, Mast Cells
Liver,
Ovary
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GS
A2B-AR cAMP
q/11
Gq
• q – heteromeric receptor
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PULMONARY:
• Vasodilation
• Mast cell release of IL-8
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• It is less widely distributed in body.
Testis
(Rat),
Mast Cerebellum, Thyroid,
Cell Brain
(Rat) Hippocampus Adrenal
Gland,
Liver
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Gi
A3-AR cAMP
Go
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Drugs
classification
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Adenosine
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• Marked hyperpolarization and suppression of calcium
dependent actions potential.
• t ½ : 10 sec.
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• Methotrexate
• Dipyridamole
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• Caffeine.mp4
• https://www.youtube.com/watch?v=YuJOh
pNS0IY
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• Nonspecific adenosine receptors antagonist.
• Competitive nonselective phosphodiesterase inhibitors.
• Use:
- CNS stimulant,
- Cardiac muscle stimulant,
- Bronchoconstriction.
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• Aminophylline
• Istradefylline
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o Anaesthesia and intensive care:
• e.g.: Remifentanil.
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o Epilepsy
• Activation of A1 receptor.
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o Parkinsons disease:
• e.g.: Istradefylline
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o Dementia and anxiety disorders
• FR 194921
o Pain
• GW 493838
o Sleep
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o Ischaemia:
• Ischaemic preconditioning
- Adenosine theory.
- Anti-inflammatory action.
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o Arrhythmia:
• e.g.: Adenocard.
o Vasodilation:
• e.g.: Adenoscan.
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o Bronchial Asthma:
• e.g.: Theophylline.
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o IBD:
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• A3 AR agonist can attenuate
apoptosis.
• e.g.: CI-IB-MECA
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• A3-AR in knockout mice had significantly lower
intraocular pressure.
• e.g.: OT-7999
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1. Gary L. Stilest, “Adenosine Receptors”, The Journal of Biological
Chemistry, (1996) 6451-6454.
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4. Catarina V. Gomes, Manuella P. Kaster, Angelo R. Tome, Paula M.
Agostinho, Rodrigo A. Cunha, “Adenosine Receptors and Brain Diseases”,
Biochimica et Biophysica Acta, (2011) 1380-1399.
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7. Stefania Gessi, Stefania Merighi, Kalia Varani, Pier Borea, “The A3
Adenosine Receptors: An Enigmatic Player in Cell Biology”,
Pharmacology and Therapeutics, (2008) 123-140.
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