Cardiac glycosides, calcium and the release of neurotransmitter from peripheral noradrenergic nerves

The requirement for external Ca (Cao) of neurotransmitter release evoked by cardenolides has been investigated in canine saphenous vein. Basal efflux of 3H-compounds from saphenous veins pre-loaded with 3H-noradrenaline was the same in the absence as in the presence of Cao; Cao is not required for basal efflux of neurotransmitter. Efflux of 3H-compounds was increased by cardenolides. Both ACS and ouabain caused a similar maximum net efflux of 3H suggesting that each evokes release from the same pool of 3H compounds. The similarity of the effects obtained with cardenolides to those obtained during exposure of saphenous vein preparations to potassium-free media suggests that 3H-efflux is the result of Na,K-ATPase inhibition. With ACS (ca. EC50) the net efflux of 3H-compounds early (less than 60 min) in the release period was greater in the absence of Cao than in its presence whereas at longer times the reverse was true; net efflux was less in the absence of Cao than in its presence. The difference in the 3H-efflux pattern was paralleled qualitatively throughout by efflux of 3H-noradrenaline. The ACS-evoked efflux of 3H-compounds in the presence and absence of Cao derives from sympathetic, noradrenergic nerves; 3H present in extraneuronal tissues was not released by the cardenolide. With ouabain (less than EC50) the total efflux of 3H over a 75 min period was greater in the absence of Cao than in its presence. The reverse was found with ouabain (greater than EC50): the total efflux of 3H was less in the absence of Cao than in its presence.(ABSTRACT TRUNCATED AT 250 WORDS)