Stimulation-evoked release of [3H]-noradrenaline by 1, 10 or 100 pulses and its modification through presynaptic alpha 2-adrenoceptors.
1 Mice isolated vasa deferentia were loaded with 1-[7,8-3H]-noradrenaline and subsequently field stimulated with 1, 10 or 100 pulses (2 ms pulse width, 1 Hz). The tritium overflow was separated into [3H]-noradrenaline and its 3H-metabolites. 2 The resting release of tritium contained about 7% [3H]-noradrenaline, 33% [3H]-3, 4-dihydroxyphenylglycol ([3H]-DOPEG) and 60% 3H-non-catechols with usually less than 1% [3H]-dihydroxymandelic acid ([3H]-DOMA). The proportion of the tritium as [3H]-noradrenaline increased with stimulation train length to 35% with 100 pulses; this increase in [3H]-noradrenaline was associated with falls in [3H]-DOPEG and 3H-non-catechols. Generally the proportional increase in [3H]-noradrenaline on stimulation was about 10 x total tritium when compared with the resting release. 3 The fractional release of [3H]-noradrenaline per pulse was independent of train length, averaging about 6 x 10(-6). This was reduced by the alpha 2-adrenoceptor agonist clonidine (0.3 - 30 nM) with an IC50 of 4.8 nM (10 pulses at 1 Hz). 4 The alpha 2-adrenoceptor antagonist, yohimbine (10 - 100 nM), did not alter the fractional release of [3H]-noradrenaline elicited by 1 pulse. The antagonist did not change the amount or composition of the resting or evoked tritium overflow. However, yohimbine (1 - 100 nM) increased the fractional release of [3H]-noradrenaline per pulse for trains of 10 or 100 pulses (1 Hz) in a concentration-dependent fashion. An increase above controls was significant only with 100 pulses and yohimbine, 30 nM. 5 The results show that the release of noradrenaline during trains of pulses in the mouse vas deferens can be regulated through presynaptic alpha 2-adrenoceptors. There was no evidence of inhibition by noradrenaline of its own release following a single pulse.
D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D014649:Vas Deferens / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine