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

Abstract

In strips of isolated canine basilar arteries, previously labeled with 3 × 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 × 10 −7−7.5 × 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 × 10 −5 M) caused an increased spontaneous 3H efflux but no longer augmented the stimulation-induced 3H overflow. Dihydroergocristine (5.4 × 10 −8−1.8 × 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 α-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.