(/sup 125/Iodo)BE 2254, a new radioligand for alpha 1-adrenoceptors
(/sup 125/cIodo)2-(beta-(14-hydroxyphenyl)-ethyl-aminomethyl)-tetralone((/sup 125/Iodo)BE 2254 or IBE 2254), a new iodinated radioligand of high specific radioactivity (2175 Ci/mmol), was synthesized and used to characterize alpha 1-adrenoceptors in rat lung and cerebral cortex membranes. The binding constants of IBE 2254, using rat lung and cortex membranes, were Kd . 53 +/- 10 pM, Bmax . 53 +/- 8 fmol/mg; and Kd . 78 +/- 14 pM, Bmas . 210 +/- 26 fmol/mg, respectively (Kd . dissociation constant of IBE 2254 determined in saturation experiments). In equilibrium binding experiments with IBE 2254, at concentrations of the free ligand up to 1.2 nM, only one class of binding sites could be detected. In kinetic experiments, the association and dissociation rate constants were 2.3 X 10(9) M-1 min-1 and 0.10 min-1, respectively. In rat cerebral cortex membranes, alpha-adrenoceptor antagonists competed for IBE 2254 binding in the following order: prazosin greater than BE 2254 greater than WB 4101 greater than phentolamine greater than corynanthine greater than yohimbine greater than rauwolscine, indicating strongly that IBE 2254 binds to alpha 1-adrenoceptors. The calculated affinities of different alpha-adrenoceptor blocking agents from inhibition of IBE 2254 binding were nearly identical in rat lung and cerebral cortex. The low dissociation constant of the ligand together with its high specific radioactivity allows binding studies to be carried out with tissue samples where only small densities of alpha 1-adrenoceptors are present.
- Research Organization:
- Pharmaceutical Division, Preclinical Research, Sandoz Ltd., Basle, Switzerland
- OSTI ID:
- 6933326
- Journal Information:
- J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States) Vol. 4 Suppl 1; ISSN JCPCD
- Country of Publication:
- United States
- Language:
- English
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551001 -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGANDS
LUNGS
MAMMALS
MEMBRANES
MORPHOLOGY
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RATS
RECEPTORS
RESPIRATORY SYSTEM
RODENTS
STEROID HORMONES
VERTEBRATES