A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors

Ihara, Masaki; Saeki, Toshihiko; Fukuroda, Takahiro; Kimura, Sachiyo; Ozaki, Satoshi; Yano, Mitsuo; Patel, A C

Title: A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors

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Abstract

A linear endothelin (ET) analog, N-acetyl-LeuMetAspLysGluAlaValTryPheAlaHisLeuAspIleIleTrp (BQ-3020), is highly selective for ET[sub B] receptors. BQ-3020 displaces [[sup 125]I]ET-1 binding to ET[sub B] receptors in porcine cerebellar membranes at a concentration 4,700 times lower than that of ET[sub A] receptors on aortic vascular smooth muscle cells (VSMC). BQ-3929 as well as ET-1 and ET-3 elicits vasoconstriction in the rabbit pulmonary artery. The ET[sub A] antagonist BB-123 failed to inhibit this BQ-3020-induced vasocontraction. Futhermore, BQ-3929 elicits endothelium-dependent vasodilation. These data indicate that BQ-3020 has ET[sub B]agonistic activity. The radioligand [[sup 125]I]BQ-3020 binds to cerebellar membranes at single high affinity sites, whereas it scarcely binds to VSMC. [[sup 125]I]BQ-3020 binding to the cerebellum was displaced by BQ-3020, ET-1 and ET-3 in a nonselective manner. However, the binding of [[sup 125]I]BQ-3020 was insensitive to the ET[sub A] antagonist BQ-123 and other bioactive peptides. Both [[sup 125]I]ET-1 and [[sup 125]I]BQ-3020 show slow onset and offset binding kinetics to ET[sub B] receptors. These data indicate that the radioligand [[sup 125]I]BQ-3020 selectively labels ET[sub B] receptors and that the slow binding kinetics of ET-1 are dependent on the peptide sequence from Leu[sup 6] to Trp[sup 21], but not on the structure formed by its two disulfide bridges.

Authors:

Ihara, Masaki; Saeki, Toshihiko; Fukuroda, Takahiro; Kimura, Sachiyo; Ozaki, Satoshi; Yano, Mitsuo ^[1]; Patel, A C ^[2]

Tsukuba Research Inst. (Japan)
Amersham International plc., Buckinghamshire (United Kingdom)

Publication Date:: Wed Jan 01 00:00:00 EST 1992

OSTI Identifier:: 7160939

Resource Type:: Journal Article

Journal Name:: Life Sciences; (United States)

Additional Journal Information:: Journal Volume: 51:6; Journal ID: ISSN 0024-3205

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; AORTA; VASOCONSTRICTION; LIGANDS; CHEMICAL COMPOSITION; PEPTIDES; RECEPTORS; ARTERIES; BIOCHEMICAL REACTION KINETICS; CELL MEMBRANES; CEREBELLUM; ENDOTHELIUM; IODINE 125; RABBITS; SWINE; TRACER TECHNIQUES; ANIMAL TISSUES; ANIMALS; BETA DECAY RADIOISOTOPES; BLOOD VESSELS; BODY; BRAIN; CARDIOVASCULAR SYSTEM; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; DAYS LIVING RADIOISOTOPES; DOMESTIC ANIMALS; ELECTRON CAPTURE RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; INTERNAL CONVERSION RADIOISOTOPES; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; NERVOUS SYSTEM; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RADIOISOTOPES; REACTION KINETICS; TISSUES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats


                    Ihara, Masaki, Saeki, Toshihiko, Fukuroda, Takahiro, Kimura, Sachiyo, Ozaki, Satoshi, Yano, Mitsuo, and Patel, A C. A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors.  United States: N. p., 1992. 
        Web.

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                    Ihara, Masaki, Saeki, Toshihiko, Fukuroda, Takahiro, Kimura, Sachiyo, Ozaki, Satoshi, Yano, Mitsuo, & Patel, A C. A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors.  United States.

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                    Ihara, Masaki, Saeki, Toshihiko, Fukuroda, Takahiro, Kimura, Sachiyo, Ozaki, Satoshi, Yano, Mitsuo, and Patel, A C. 1992.  
        "A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors".  United States.

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@article{osti_7160939,

  title        = {A novel radiologand [[sup 125]I]BQ-3020 selective for endothelin (ET[sub B]) receptors},

  author       = {Ihara, Masaki and Saeki, Toshihiko and Fukuroda, Takahiro and Kimura, Sachiyo and Ozaki, Satoshi and Yano, Mitsuo and Patel, A C},

  abstractNote = {A linear endothelin (ET) analog, N-acetyl-LeuMetAspLysGluAlaValTryPheAlaHisLeuAspIleIleTrp (BQ-3020), is highly selective for ET[sub B] receptors. BQ-3020 displaces [[sup 125]I]ET-1 binding to ET[sub B] receptors in porcine cerebellar membranes at a concentration 4,700 times lower than that of ET[sub A] receptors on aortic vascular smooth muscle cells (VSMC). BQ-3929 as well as ET-1 and ET-3 elicits vasoconstriction in the rabbit pulmonary artery. The ET[sub A] antagonist BB-123 failed to inhibit this BQ-3020-induced vasocontraction. Futhermore, BQ-3929 elicits endothelium-dependent vasodilation. These data indicate that BQ-3020 has ET[sub B]agonistic activity. The radioligand [[sup 125]I]BQ-3020 binds to cerebellar membranes at single high affinity sites, whereas it scarcely binds to VSMC. [[sup 125]I]BQ-3020 binding to the cerebellum was displaced by BQ-3020, ET-1 and ET-3 in a nonselective manner. However, the binding of [[sup 125]I]BQ-3020 was insensitive to the ET[sub A] antagonist BQ-123 and other bioactive peptides. Both [[sup 125]I]ET-1 and [[sup 125]I]BQ-3020 show slow onset and offset binding kinetics to ET[sub B] receptors. These data indicate that the radioligand [[sup 125]I]BQ-3020 selectively labels ET[sub B] receptors and that the slow binding kinetics of ET-1 are dependent on the peptide sequence from Leu[sup 6] to Trp[sup 21], but not on the structure formed by its two disulfide bridges.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/7160939},
  journal      = {Life Sciences; (United States)},

  issn         = {0024-3205},

  number       = ,

  volume       = 51:6,

  place        = {United States},

  year         = {Wed Jan 01 00:00:00 EST 1992},

  month        = {Wed Jan 01 00:00:00 EST 1992}

}

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