Summary
Dog saphenous vein strips were incubated with 1.4 μmol/l 3H-(-)-noradrenaline for 60 min, after inhibition of the noradrenaline-metabolizing enzymes and of extraneuronal uptake. At the end of the incubation period the strips were perifused for 150 min; cocaine (10 μmol/l) was added to the perifusion fluid from t=75 min onwards. In some experiments either phentolamine (10 μmol/l) or clonidine (0.1 μmol/l) was also added at this time. Some strips were subjected to electrical stimulation from t=100 to 150 min of perifusion (t=0 being the start of perifusion), with frequencies ranging from 0.5 to 13.5 Hz. A compartmental analysis of spontaneous or electrically-induced efflux of 3H-noradrenaline was made. The spontaneous efflux had a long half time (t/2=124 min) and most of the 3H-noradrenaline which had accumulated in the strips did not participate in the efflux (“bound fraction”, representing 90% of tissue activity at t=100 min of perifusion). Neither phentolamine nor clonidine modified the half time or the “bound fraction” observed for spontaneous efflux. Electrical stimulation (>0.5 Hz) mobilized only one compartment of noradrenaline, which represented about 50% of the noradrenaline accumulated in the strips. The half time of 3H-efflux induced by electrical stimulation decreased when the frequency increased from 0.5 Hz up to 13.5 Hz. Phentolamine increased the rate of efflux for all frequencies of stimulation and decreased the half time of efflux. However, the releasable pool of noradrenaline was only increased by phentolamine at 0.5 Hz, but not at higher frequencies. Clonidine was used only at two frequencies of stimulation, 1.5 and 4.5 Hz. For the low frequency clonidine decreased the releasable pool, but no change was observed at 4.5 Hz.
The results support the view that there is a norarenaline pool which is resistant to electrical stimulation and that its magnitude is not dependent on the activity of presynaptic α-adrenoceptors.
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Results presented in part to the 13th Annual Meeting of the Portuguese Pharmacological Society (Porto, December 1982) and to the 5th Meeting on Adrenergic Mechanisms (Porto, October 1983)
Work supported by a grant from Instituto Nacional de Investigação Científica (FmPl)
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Brandão, F., Davidson, R. & Monterio, J.G. A kinetic study of the release of noradrenaline by electrical stimulation: influence of presynaptic α-adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 248–252 (1985). https://doi.org/10.1007/BF00515549
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DOI: https://doi.org/10.1007/BF00515549