DUAL EFFECT OF MUSCARINIC RECEPTOR AGONISTS ON CA2-SY5Y NEUROBLASTOMA-CELLS( MOBILIZATION IN SH)

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: carbamoyl choline, acetylcholine, propionylcholine, butyrylcholine, acetylthioch oline, methylfurmethide and tetrametylammonium. The dose-response curv es reached a clear maximum followed by a downturn of the curve. The co ncentration interval where the activatory and inhibitory effects occur ed depended on the structure of the ligand. The bell-shaped dose-respo nse curves were analysed assuming that the drugs interact with two sit es, which are responsible for agonistic and antagonistic effects, on t he muscarinic receptors. The results indicate that full vs. partial ag onism is at least in part determined by relative affinities of these t wo sites.