Abstract
The aim of this study was to investigate the effect of a calmodulin antagonist, calmidazolium, on the muscarinic receptor-mediated increase in inositol 1,4,5-trisphosphate [I(1,4,5)P3] in SH-SY5Y cells. Exposure to 10 microM calmidazolium suppressed the initial I(1,4,5)P3 peak increase (IC50 1 microM) whereas the steady-state was less affected. Furthermore, calmidazolium displayed non-competitive antagonistic properties of [3H]quinuclidinyl benzylate binding to intact SH-SY5Y cells and to membranes from these cells. These effects were also obtained with another calmodulin inhibitor, trifluoperazine (10 microM). These results demonstrate that novel finding that the calmodulin inhibitors calmidazolium and trifluoperazine act as non-competitive muscarinic antagonists in SH-SY5Y cells and inhibit muscarinic receptor-stimulated phospholipase C activation in these cells.
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