Dual effect of muscarinic receptor agonists on Ca2+ mobilization in SH-SY5Y neuroblastoma cells

• Published in: European journal of pharmacology 1995-09, Vol.291 (1), p.43-50
• Main Authors: JÄRV, J, HAUTALA, R, AKERMAN, K. E. O
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain Neoplasms - metabolism; Calcium - metabolism; Cell receptors; Cell structures and functions; Culture Media; Fundamental and applied biological sciences. Psychology; Humans; Kinetics; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Neuroblastoma - metabolism; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Spectrometry, Fluorescence; Tumor Cells, Cultured
• ISSN: 0922-4106; 0014-2999
• DOI: 10.1016/0922-4106(95)90187-6

The muscarinic receptor-stimulated mobilisation of calcium ions in SH-SY5Y neuroblastoma cells was measured as function of the concentration of seven muscarinic receptor agonists and partial agonists: carbamoylcholine, acetylcholine, propionylcholine, butyrylcholine, acetylthiocholine, methylfurmethide and tetrametylammonium. The dose-response curves reached a clear maximum followed by a downturn of the curve. The concentration interval where the activatory and inhibitory effects occurred depended on the structure of the ligand. The bell-shaped dose-response curves were analysed assuming that the drugs interact with two sites, which are responsible for agonistic and antagonistic effects, on the muscarinic receptors. The results indicate that full vs. partial agonism is at least in part determined by relative affinities of these two sites.