Effects of Iskedyl and its two constituents raubasine and dihydroergocristine on the release of [3H]noradrenaline and [3H]serotonin in canine basilar arteries.

In strips of isolated canine basilar arteries, previously labeled with 3 X 10(-7) M of either [3H]noradrenaline or [3H]serotonin, three consecutive periods of electrical stimulation (2 Hz) evoked a reproducible overflow of the respective [3H]amine. Increasing concentrations of raubasine (7.5 X 10(-7)-7.5 X 10(-6) M) did not influence the spontaneous 3H efflux but increased the stimulation-induced 3H overflow in a concentration-dependent way. The highest concentration of raubasine used (2.5 X 10(-5) M) caused an increased spontaneous 3H efflux but no longer augmented the stimulation-induced 3H overflow. Dihydroergocristine (5.4 X 10(-8)-1.8 X 10(-6) M) did not affect the spontaneous 3H efflux; the compound slightly but significantly reduced the stimulation-evoked 3H overflow concentration dependently. High concentrations of Iskedyl (mixtures of raubasine and dihydroergocristine in a 14:1 molar ratio) augmented the spontaneous 3H efflux and moderately decreased the stimulation-induced 3H overflow. Although some quantitative differences were noted, the compounds exerted similar effects on arteries labeled with either [3H]noradrenaline or [3H]serotonin. The most important difference detected was that DHEC decreased the stimulation-induced release of [3H]serotonin more than that of [3H]noradrenaline. Our results allow a comparison of [3H]noradrenaline and [3H]serotonin release in the dog basilar artery: the basal fractional release of [3H]serotonin was higher than that of [3H]noradrenaline while the stimulation-induced overflow was equal in both groups of tissues. The constituents of Iskedyl can profoundly affect the release of the neurotransmitters. Raubasine, a presynaptic alpha-receptor antagonist, increases the stimulation-induced release of the neurotransmitters and both DHEC, a presynaptic receptor agonist, and the combination of the compounds, Iskedyl, decrease the release of the neurotransmitters.