抄録
The effects of W-7, W-5, No. 233, and chlorpromazine on sympathetic nerve transmitter efflux were compared in superfused canine basilar arterial preparations preloaded with [3H] -norepinephrine. In vitro experiments suggest that these agents are selective calmodulin antagonists. The electrical transmural stimulation-induced efflux of tritium was reduced by W-7 and W-5, although they were unexpectedly equipotent since W-5 is a chloride-deficient derivative of W-7 and has a lower affinity for calmodulin than does W-7. The median inhibitory concentration (IC50) of W-7 for stimulation-induced efflux was 3.4×10-6 M. The addition of No. 233 at relatively high concentrations (3×10-5 M and 5×10-5 M) caused a reduction in stimulation-induced efflux. Chlorpromazine produced a dual effect on the efflux: enhancement at low concentrations (below l×10-6 M) and reduction at high concentrations. The IC50 values of No. 233 and chlorpromazine were 3.5×10-5 M and 2.5×10-5 M, respectively. The additions of these four agents also caused a significant elevation in the spontaneous basal efflux of tritium from the preparations. The concentrations of the agents that elevated the spontaneous efflux to the level of half the stimulationinduced efflux were closely fitted to the IC50 values for stimulation-induced efflux. This finding indicates that the elevation in spontaneous efflux is directly proportional to the reduction in electrical stimulation-induced efflux. From these findings, it is concluded that naphthalenesulfonamides including W-7 have a direct effect on sympathetic nerve terminals which is independent of the effect on calmodulin.
