(-)(125I)-iodopindolol, a new highly selective radioiodinated beta-adrenergic receptor antagonist: measurement of beta-receptors on intact rat astrocytoma cells
(-)-Pindolol, one of the most potent beta-adrenergic receptor antagonists, was radioiodinated using chloramine-T oxidation of carrier-free Na 125I and separated from unreacted pindolol to yield 2200 Ci/mmole (-)-(125I)-iodopindolol ((-)-(125I)-IPin). Mass and ultraviolet spectra confirmed that the iodination occurred on the indole ring, presumably at the 3 position. The binding of radiolabeled (-)-(125I)-IPin to beta-adrenergic receptors has been studied using intact C6 rat astrocytoma cells (2B subclone) grown in monolayer cultures. Binding of (-)(125IPin was saturable with time and concentration. Using 13 pM (-)-(125I)IPin, binding equilibrium was reached in 90 min at 21-22 degrees C. The reverse rate constant was 0.026 min-1 at 21/sup 0/C. Specific binding (expressed as 1 microM(-)-propranolol displaceable counts) of (-)-(125I)-IPin was 95% of total binding. Scatchard analysis of (-)-(125I)-I)Pin binding revealed approximately 4300 receptors/cell and a dissociation constant of 30 pM. This was in excellent agreement with the kinetically determined dissociation constant of 35 pM. Displacement by propranolol and isoproterenol showed that (-)-(125I)-IPin binding sites were pharmacologically and stereospecifically selective. These results indicate that (-)-(125I)-IPin, a pure (-)-stereoisomer, high specific activity radioligand, selectively binds to beta-adrenergic receptors in whole cells with a high percentage of specific binding and should therefore be useful in the study and measurement of cellular beta-adrenergic receptors.
- OSTI ID:
- 5873904
- Journal Information:
- J. Cyclic Nucleotide Res.; (United States), Journal Name: J. Cyclic Nucleotide Res.; (United States) Vol. 6:4; ISSN JCNRD
- Country of Publication:
- United States
- Language:
- English
Similar Records
Structural derivatives of pindolol: relationship between in vivo and in vitro potencies for their interaction with central beta-adrenergic receptors
Characterization and regulation of. beta. /sub 2/-adrenergic receptors in rat vas deferens
Related Subjects
400702 -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550201* -- Biochemistry-- Tracer Techniques
550301 -- Cytology-- Tracer Techniques
560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CELL CULTURES
CHEMICAL PREPARATION
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
NERVE CELLS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHARMACOLOGY
PROPANOLS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
SYNTHESIS
VERTEBRATES