Comparative binding studies with cholinergic ligands and histrionicotoxin at muscarinic receptors of neural cell lines.

摘要: [3H]Scopolamine and [3H]quinuclidinyl-benzilate (QNB) have been used to study inhibitory acetylcholine receptors of neuroblastoma clone N1E-115 excitatory NG108-15 x glioma hybrid cells. Both [3H]ligands bind with high affinity muscarinic the The apparent dissociation constants are 0.4 nM (N1E-115) 0.5 (NG108-15) for [3H]scopolamine, 0.06 0.1 [3H]QNB. receptor concentration is 25 fmol/mg in 40 NG108-15. Binding release [3H]-scopolamine kinetically biphasic processes. [3H]QNB has a similar rate binding but much slower from receptor. both competitively inhibited by compounds known interact receptors. With 1 [3H]ligand 50% inhibition caused nanomolar concentrations antagonists, 100 micromolar agonists, >100 nicotinic cholinergic compounds. Slopes approximately were found antagonists agonists logit-log plots competition data. Antagonist can therefore be described as interaction noncooperative class receptors, whereas agonist exhibits negative cooperativity or heterogeneity sites. dihydroiso-histrionicotoxin (H2-HTX) cells also studied experiments. H2-HTX inhibits [3H]scopolamine noncompetitive manner causing at an applied 70 µM. local anesthetic, tetracaine, shows almost identical characteristics. Dihydro-adaline, granatan-3β-ol granatan-3α-ol less strong inhibitors. Structural comparison these suggests that two aliphatic side chains proximity hydroxyl amino groups may important features