A peptide ETB receptor agonist
IRL 1620 is a peptide endothelin type B (ETB) receptor agonist.1 It selectively binds to ETB receptors (Ki = 16 pM) over ETA receptors (IC50 = 1.9 ?M) and induces contraction of isolated guinea pig trachea when used at concentrations ranging from 0.01 to 1 ?M. IRL 1620 (1 nmol/kg) reduces mean arterial pressure (MAP) in normotensive rats and spontaneously hypertensive rats (SHRs) and diminishes the transient depressor response in SHRs.2 It reduces infarct volume and improves motor and neurological function in a rat model of cerebral ischemia.3 IRL 1620 also improves spatial memory deficits induced by amyloid-β (Aβ) in a rat model of Alzheimer's disease.
1.Takai, M., Umemura, I., Yamasaki, K., et al.A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptorBiochem. Biophys. Res. Commun.184(2)953-959(1992) 2.James, A.F., Urade, Y., Webb, R.L., et al.IRL 1620, succinyl-[Glu9,Ala11,15]-endothelin-1(8-21), a highly specific agonist of the ETB receptorCardiovasc. Drug Rev.11(3)253-270(1993) 3.Gulati, A., Hornick, M.G., Briyal, S., et al.A novel neuroregenerative approach using ETB receptor agonist, IRL-1620, to treat CNS disordersPhysiol. Res.67(Suppl 1)S95-S113(2018)
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Kinase experiment: |
The plasma membrane of porcine lung (2 ug of protein) is incubated at 37°C for 1 hr with 30 pM [125I]ET-1 or 10 pM [125I]ET-3 in the absence or presence of various amounts of nonlabeled ligands (IRL-1620) in a total volume of 1 mL of assay buffer. After the incubation, unbound [125I]ETs are separated and radioactivity in the membrane pellet is measured in an autogamma counter[1]. |
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Animal experiment: |
Rats: Specific ETB receptor agonist, IRL-1620 (5 μg/kg) and specific ETB receptor antagonist, BQ788 (1 mg/kg) are administered intravenously (i.v.) on day 8. IRL-1620 is administered on day 8 three times at a dose of 5 μg/kg, i.v. at 2-h intervals between each injection[2]. Mice: Tolerance to morphine is induced using a 3-day cumulative dosing regimen. Morphine treatment schedule consisted of twice-daily s.c. injections of morphine for three days given at (i) 30 mg/kg (a.m.) and 45 mg/kg (p.m.) on day 1; (ii) 60 mg/kg (a.m.) and 90 mg/kg (p.m.) on day 2; and (iii) 120 mg/kg twice (a.m. and p.m.) on day 3. The IRL-1620 treatment schedule consists of three times-daily injections of IRL-1620 for two days given at 5 μg/kg, i.v. spaced apart every 2 h on days 1 and 3. At the end of the treatment schedule, a challenge dose of morphine (5 mg/kg, s.c.) is administered on day 4 to assess tolerance[3]. |
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参考文献: [1]. Takai M, et al. A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochem Biophys Res Commun. 1992 Apr 30;184(2):953-9. |
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