CALMIDAZOLIUM INHIBITS MUSCARINIC RECEPTOR-MEDIATED PLC ACTIVATION INSH-SY5Y CELLS

THE aim of this study was to investigate the effect of a calmodulin an tagonist, calmidazolium, on the muscarinic receptor-mediated increase of inositol 1,4,5-trisphosphate [I(1,4,5)P-3] in SH-SY5Y cells. Exposu re to 10 mu M calmidazolium suppressed the initial I(1,4,5)P-3 peak in crease (IC50 1 mu M) whereas the steady-state was less affected. Furth ermore, calmidazolium displayed non-competitive antagonistic propertie s of [H-3]quinuclidinyl benzylate binding to intact SH-SY5Y cells and to membranes from these cells. These effects were also obtained with a nother calmodulin inhibitor, trifluoperazine (10 mu M). These results demonstrate the novel finding that the calmodulin inhibitors calmidazo lium and trifluoperazine act as non-competitive muscarinic antagonists in SH-SY5Y cells and inhibit muscarinic receptor-stimulated phospholi pase C activation in these cells.