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

Journal Article · Wed Jan 01 00:00:00 EST 1992 · Life Sciences; (United States)

OSTI ID:7160939

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

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

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.

• OSTI ID: 7160939
• Journal Information: Life Sciences; (United States), Vol. 51:6; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

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