Open AccessBinding characteristics of (3H)quinupramine to rat brain membrane fractions.
Author(s) -
Hirohiko Sakamoto,
Nobuharu Yokoyama,
Tetsuya Nishimoto,
Kazuyuki Murai,
Hiroshi Tazaki,
Shigekatsu Kohno,
Katsuya Ohata
Publication year - 1987
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.45.27
Subject(s) - muscarinic acetylcholine receptor , quinuclidinyl benzilate , binding site , chemistry , population , biophysics , cerebellum , synaptosome , cholinergic , receptor , membrane , biochemistry , biology , medicine , endocrinology , demography , sociology
The binding characteristics of [3H]quinupramine to rat brain membrane fractions were studied. The specific binding of [3H]quinupramine to rat brain membrane fractions was stable, reversible and saturable. Scatchard analysis of the data from saturation experiments indicated that the specific binding was a single population with an affinity (KD) of 3.04 nM, a maximal binding site number (Bmax) of 714 fmol/mg protein, and a Hill coefficient (nH) of 1.08. Compounds known to inhibit muscarinic cholinergic receptors such as atropine and quinuclidinyl benzilate were the most potent competitors of [3H]quinupramine binding. When the drug potencies in inhibiting [3H]quinupramine binding were tested in the presence of 10 nM atropine, mianserin was the most potent competitor. Studies of the subcellular fractions showed that there was an enrichment of [3H]quinupramine binding sites in the synaptosome fraction. The regional distribution study revealed the highest densities of binding sites in the cerebral cortex and the lowest in the cerebellum. Thus, the specific binding of [3H]quinupramine observed here can be accounted for by both muscarinic cholinergic and serotonin S2 receptors.