Abstract
The effect of guanidine alkyl derivatives on the evoked release of [3H]norepinephrine [( 3H]NE) from spleen strips was examined. Guanidine, methyl guanidine and N,N-dimethyl guanidine all enhanced the field-stimulated release of [3H]NE 2- to 3-fold, whereas N,N'-dimethyl guanidine and propyl guanidine were without effect. The latter compound blocked the stimulatory effect of an equimolor concentration (4 mM) of guanidine. Guanidine enhanced moderately the field-stimulated release of [3H]NE from spleen strips pretreated with phenoxybenzamine. The efflux of [3H]NE from spleen slices induced by calcium ionophore A-23187 was not altered by guanidine incubation. The effect of guanidine on intracellular calcium movement was also tested by monitoring the effect of the drug on evoked secretion of ATP from human platelets. Guanidine did not modify this release. It is concluded that guanidine and its active structural derivatives augment [3H]NE release by increasing the influx of calcium through the voltage-sensitive calcium channels, but not by the mobilization of intracellular calcium pools. The biochemical basis for the action of the guanidinium cation is discussed.
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