1. Seminar on Endothelin Receptors
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Prepared by-
Kunj M. Patel,
M. Pharm ,sem-1
Roll no - 01
Guided by-
Dr. N. N. Shah,
A. R. College of Pharmacy &
G. H. Patel Institute of Pharmacy, V. V. Nagar

2.  Introduction
 Classification of endothelin receptors
 Location of endothelin receptors
 Signal transduction mechanism of endothelin receptors
 Physiological functions of endothelin receptors
 Agonists of endothelin receptors
 Antagonists of endothelin receptors
 Adverse effects of endothelin receptor antagonists
 References
Contents
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3.  Endothelin is a very potent vasoconstrictor peptide
derived from the endothelial cells of vasculature.
 After the discovery of the endothelium-derived
relaxing factor, a contracting factor was isolated from
bovine aortic and pulmonary endothelium. Its gene
sequence was identified in 1987, and it was named
endothelin (ET).
 ET is a family of four 21-amino acid peptides, i.e., ET-1,
ET-2, ET-3 and ET-4 (vasoactive intestinal constrictor).
Introduction
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4.  ET-1 is a potent vasoconstrictor.
 In addition to their cardiovascular effects, ETs are
involved in embryonic development,
bronchoconstriction, prostate growth,
carcinogenesis, and gastrointestinal and endocrine
function.
Continue…...
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5.  Endothelin receptors are classified in to:
Endothelin receptor type-A
Endothelin receptor type-B
Classification Of Endothelin Receptors
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6.  Endothelin receptor type-A
ETA
 Endothelin receptor type-B
ETB1
ETB2
Subtypes
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7.  Endothelin receptor type-A are located on vascular smooth
muscle cells , brain , lungs , kidney and adrenal gland
 Endothelin receptors type-B are located on endothelial cells
lining the vessel wall
 Endothelin receptors have also been found in the brain, e.g.
cerebral cortex, cerebellum and glial cells.
Location Of Endothelin Receptors
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8. Figure no -1
Actions of endothelin-1
through its receptors.
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9.  Both ET 𝐴 and ETB receptor subtypes are G- protein coupled
receptors.
 ETA response:
 As shown in figure , the signal transduction mechanisms
include :
Opening of ca2+ channels through phospholipase
C/IP3 pathway
↓
increase in intracellular ca2+
↓
results in vasoconstriction
Signal Transduction Mechanism Of
Endothelin Receptors
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10.  ETB response:
An activation of phospholipase A2 (which
produce PGI2) and of nitric oxide synthase leading
to vasodilation.
 ETA and ETB response:
Activation of protein kinase –c
through phospholipase C/DAG pathway .
leading to mitogenesis and also leading
to vasoconstriction.
ETB Response And ETA And ETB
Response
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11.  ETA is a subtype for vasoconstrictionThese receptors are
found in the smooth muscle tissue of blood vessels, and
binding of endothelin to ETA increases vasoconstriction
and the retention of sodium, leading to increased blood
pressure.
 ETB1 mediates vasodilation, When endothelin binds to ETB1
receptors, this leads to the release of nitric oxide (also
called endothelium-derived relaxing factor), natriuresis and
diuresis and mechanisms that lower blood pressure.
Physiological Functions Of
Endothelin Receptors
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12.  ETB2 mediates vasoconstriction
 ET receptor are also found in the nervous system
where they may mediate neurotransmission and
vascular functions.
Continue…..
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13. Figure no -2: characteristic features of endothelin receptors.
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14.  Endothelin 1:-
Selective agonist for ETB receptors.
 Endothelin 2:-
Potent vasoconstrictor from vascular
endothelial cells; displays similar selectivity for
ETA and ETB receptors
Agonists Of Endothelin Receptors
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15.  Endothelin 3:-
Vasoconstrictor from vascular endothelial cells;
preferred agonist for ETB receptors.
 Sarafotoxin:-
ETB agonist; toxin with strong vasoconstrictor activity
ETA agonist; increases intracellular Ca2+
Continue…..
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16.  Many selective as well as non- selective antagonists
have been developed.
 Selective ETA receptor antagonists
• sitaxsentan
• ambrisetan
these drugs are currently under trials.
 Selective ETB receptor antagonists
• IRL-1038
Antagonists Of Endothelin receptors
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17.  Non selective antagonists
• Bosentan
this drug is active both I.V. and orally . blocks both
ETA and ETB.
 Other antagonists
• Phosphoramidon
it acts by inhibiting endothelin converting enzyme
so, the inhibition of formation of endothelin -1
occurs.
Continue…..
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18.  Fall in BP
 Tachycardia
 Headache
 Gastric upset
 Teratogenic effects
Adverse Effects Of Endothelin
Antagonists
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19. 1. Sharma H.L., sharma K.K., “principles of pharmacology”, Paras
medical publisher, New Delhi, 2nd edition, 2011, page no:242-244
2. http://circ.ahajournals.org/content/102/19/2434.full
3. http://www.ebi.ac.uk/interpro/entry/IPR000499
4. http://en.wikipedia.org/wiki/Endothelin_receptor_type_A
5. http://en.wikipedia.org/wiki/Endothelin_receptor_antagonist
6. http://en.wikipedia.org/wiki/Endothelin_receptor
7. http://www.sigmaaldrich.com/life-science/biochemicals/biochemical-
products.html?TablePage=111029074
8. http://www.pharmacorama.com/en/Sections/Angiotensin_6.php
9. http://www.cvpharmacology.com/vasodilator/ETblockers.htm
10. http://en.wikipedia.org/wiki/Endothelin_receptor_type_B
References
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20. THANK YOU
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