Affordable Access

Publisher Website

Comparison of two radiolabeled quinuclidinyl benzilate ligands for the characterization of the human peripheral lung muscarinic receptor

Life Sciences
Publication Date
DOI: 10.1016/0024-3205(87)90724-7
  • Biology


Abstract Quinuclidinyl benzilate, a muscarinic antagonist, has previously been used in its tritiated form ([ 3H]-QNB) to study the lung muscarinic receptor. We investigated whether a newer iodinated form of QNB ([ 125I]-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°C. At 37°C the specific binding of [ 3H]-QNB increased slightly, but no specific binding of [ 125I]-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 and a receptor concentration of 34 ± 3 fmol/mg protein. The iodinated QNB identified a single higher affinity human lung binding site (Kd = 0.27 ± 0.32 pM) of much smaller quantity (0.62 ± 0.06 fmol/mg protein). Competition studies comparing the binding of unlabeled QNB relative to labeled QNB indicated that unlabeled QNB had the same Kd as that measured for [ 3H]-QNB, but a 5 log greater Kd than that measured for [ 125I]-QNB. Other muscarinic receptor agonists and antagonists competed with [ 3H]-QNB, but not [ 125I]-QNB for binding to muscarinic receptors with the expected magnitude and rank order of potency. We conclude that of the 2 radiolabeled forms of QNB available, only the tritiated form should be used to study the human peripheral lung muscarinic receptor.

There are no comments yet on this publication. Be the first to share your thoughts.