VARIATION IN NORADRENALINE OUTPUT WITH CHANGES IN STIMULUS FREQUENCY AND TRAIN LENGTH: ROLE OF DIFFERENT NORADRENALINE POOLS

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Abstract
1 During adrenergic nerve stimulation the output/pulse of noradrenaline from the rabbit vas deferens and portal vein is not constant but increases as the stimulus frequency or train length is increased. Depending upon the stimulus frequency and train length the fractional release of noradrenaline may vary from less than 10−7 to greater than 10−4. 2 Endogenous tissue stores of noradrenaline were labelled by incubation with (–)-[3H]-noradrenaline and [14C]-tyrosine. The output/pulse of newly synthesized [14C]-noradrenaline remained constant as the train length was increased whilst the output/pulse of [3H]-noradrenaline increased under the same conditions. This phenomenon was independent of the stimulus frequency. Newly synthesized noradrenaline also appeared in the superfusate following nerve stimulation more rapidly than exogenously loaded noradrenaline. 3 Both [3H]-noradrenaline and [14C]-tyrosine were found to label an easily releasable store of noradrenaline. Mobilization from this store was the same at low and high frequencies of nerve stimulation. 4 It is concluded that at least two functional stores of noradrenaline exist within the adrenergic nerve ending. Newly synthesized noradrenaline is probably only a minor constituent of transmitter output under normal conditions of adrenergic nerve activity. 5 At least two mechanisms control the amount of noradrenaline released per pulse during nerve stimulation. Facilitation of release with increasing train lengths appears to be due to the mobilization of transmitter from a secondary store. Facilitation of release with increasing stimulus frequency is not dependent on mobilization from any particular store and at present there is no satisfactory explanation for this phenomenon.