Comparison of two radiolabeled quinuclidinyl benzilate ligands for the characterization of the human peripheral lung muscarinic receptor
Quinuclidinyl benzilate, a muscarinic antagonist, has previously been used in its tritiated form ((/sup 3/H)-QNB) to study the lung muscarinic receptor. The authors investigated whether a newer iodinated form of QNB ((/sup 125/I)-QNB) of higher specific activity would be an appropriate ligand to study the human peripheral lung muscarinic receptor. Both the tritiated and iodinated ligands bound specifically to human lung at 23/sup 0/C. At 37/sup 0/C the specific binding of (/sup 3/H)-QNB increased slightly, but no specific binding of (/sup 125/I)-QNB was found. The data from multiple equilibrium binding experiments covering a wide range of radiolabeled QNB concentrations were combined and analyzed using the computer modeling program, LIGAND. The tritiated QNB identified a single affinity human lung binding site with a Kd of 46 +/- 9 pM. The iodinated QNB identified a single higher affinity human lung binding site of much smaller quantity. Competition studies comparing the binding of unlabeled QNB relative to labeled QNB indicated that unlabeled QNB had the same Kd as that measured for (/sup 3/H)-QNB, but a 5 log greater Kd than that measured for (/sup 125/I)-QNB. Other muscarinic receptor agonists and antagonists competed with (/sup 3/H)QNB, but not (/sup 125/I)-QNB for binding to muscarinic receptors with the expected magnitude and rank order of potency. 17 references, 2 figures, 2 tables.
- Research Organization:
- VA Medical Center, Iowa City, IA
- DOE Contract Number:
- AS05-82ER60039
- OSTI ID:
- 6080649
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 41:13; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Characterization of muscarinic cholinergic receptor subtypes in human peripheral lung
Characterization of the muscarinic cholinoceptors in the human detrusor
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
AFFINITY
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BENZOIC ACID
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACID ESTERS
CARBOXYLIC ACIDS
COMPARATIVE EVALUATIONS
COMPUTERIZED SIMULATION
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGANDS
LUNGS
MAMMALS
MAN
MEMBRANE PROTEINS
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PRIMATES
PROTEINS
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RESPIRATORY SYSTEM
SIMULATION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES