The effects of (-)-daurisoline on Ca2+ influx in presynaptic nerve terminals.

1. The effects of (-)-daurisoline on 45Ca2+ uptake and [3H]-gamma-aminobutyric acid ([3H]-GABA) release from synaptosomes of rat cerebral cortex and on contractile activity of rat aorta were examined. 2. Application of (-)-daurisoline (1-100 microM) produced concentration-related inhibition of high K(+)-stimulated 45Ca2+ uptake and [3H]-GABA release (IC50 = 7.7 +/- 0.9 microM and 10.0 +/- 1.5 microM, respectively) in synaptosomes but verapamil was only weakly active. 3. Neither (-)-daurisoline (100 microM) nor verapamil (100 microM) modified 45Ca2+ uptake in control medium (5 mM K+, resting uptake) and [3H]-GABA release in Ca-free medium (45 mM K+ basal release). 4. High K+ and noradrenaline-evoked contractions of rat aorta were inhibited by both (-)-daurisoline and verapamil. 5. In conclusion, (-)-daurisoline, which differed from verapamil in its mode of blocking Ca2+ influx may be a potent Ca2+ antagonist of Ca2+ channels in neurones.