Effects of l-stepholidine on synaptosomal Ca(2+)-ATPase and subcellular calmodulin in rat striatum.

Our results showed that l-stepholidine (l-SPD) inhibited basal Ca(2+)-ATPase activity in rat striatal synaptosomes with an IC50 of 31.5 mumol.L-1, suggesting its interaction with Ca2+ transport. l-SPD inhibited also calmodulin (CaM)-activated basal Ca(2+)-ATPase in a concentration-dependent manner. A complete reversal of CaM activation of Ca(2+)-ATPase was observed with l-SPD 10 mumol.L-1. The activity of synaptosomal Ca(2+)-ATPase and membrane-bound CaM level were decreased in haloperidol (1 mg.kg-1.d-1, ip) and l-SPD (5, 10, and 30 mg.kg-1.d-1, ip) treated rats for 7 and 14 d, respectively. But the activity of Ca(2+)-ATPase and membrane CaM level were increased after treatment with the same of doses haloperidol and l-SPD for 21 d. During the treatments with haloperidol and l-SPD cytosolic and nuclear CaM levels were not altered. These results suggest that l-SPD may modulate the release and synthesis of dopamine (DA) and the negative feedback regulation of presynaptic DA receptors by altering Ca2+ and CaM regulating processes in the central dopaminergic nervous system.