Alteration of norepinephrine release from (3H)-norepinephrine preloaded basilar artery by naphthalenesulfonamides.

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Abstract
The effects of W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] W-5 [N-(6-aminohexyl)-1-naphthalene sulfonamide], No. 233 [2-N-dansyl-L-arginine-4-tert-butylpiperidine amide] 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 3H 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 .times. 10-6 M. The addition of No. 233 at relatively high concentrations (3 .times. 10-5 and 5 .times. 10-5 M) caused a reduction in stimulation-induced efflux. Chlorpromazine produced a dual effect on the efflux: enhancement at low concentrations (below 1 .times. 10-6 M) and reduction at high concentrations. The IC50 values of No. 233 and chlorpromazine were 3.5 .times. 10-5 M and 2.5 .times. 10-5 M, respectively. The additions of these 4 agents also caused a significant elevation in the spontaneous basal efflux of 3H from the preparations. The concentrations of the agents that elevated the spontaneous efflux to the level of half the stimulation-induced efflux were closely fitted to the IC50 values for stimulation-induced efflux. The elevation in spontaneous efflux is directly proportional to the reduction in electrical stimulation-induced efflux. Naphthalenesulfonamides including W-7 have a direct effect on sympathetic nerve terminals which is independent of the effect on calmodulin.