Record 1 of 1 in BA on CD July - December 1990

Title

Properties of a quinuclidinyl benzilate binding component in the bulb mite.

Author(s)

HUANG-Z; KNOWLES-C-O

Source Journal

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C COMPARATIVE PHARMACOLOGY AND TOXICOLOGY 95(1): 71-78

Publication Year

1990

Language of Article

English

Abstract

1. About 95% of the specific binding (defined by atropine) of the muscarinic ACh receptor antagonist (3H)-quinuclidinyl benzilate occurred in the low speed pellet (5500 g, 10 min) of whole bulb mite homogenates and was heat sensitive, linear with tissue concentrations and saturable. Rosenthal analysis indicated that (3H)QNB was binding with high affinity (K-d 474 pM) to a single class of low density (B-max 202 fmol g-1) binding sites; the Hill coefficient was 1.0. 2. Kinetic studies revealed that binding was rapid and reversible, with association (k+1) and dissociation (k-1) rate constants of 7.8 times 10-5 sec-1 M-1 and 3.1 times 10-4 sec-1, respectively. The K-d from kinetic data (k-1/k+1) was 414 pM. 3 Muscarinic drugs generally were much more potent than were nicotinic drugs as inhibitors of (3H)QNB binding, and muscarinic antagonists generally were more potent than were agonists. 4. Binding was stereoselective because R (-)QNB was about 10,000 times more potent than S(+)-QNB, and dexetimide was about 1000 times more potent than its enantiomer levetimide as inhibitors of (3H)QNB binding. 5. Pirenzepine, a selective antagonist of mammalian M-1 muscarinic receptors was very effective in protecting against (3H)QNB binding, whereas methoctramine, a selective antagonist of M-2 muscarinic receptors, was much less effective. 6. Altogether these data suggest that the specific binding of (3H)QNB is most likely to a population of putative muscarinic ACh receptors, probably of the M-1 subtype. .