Release and turnover of noradrenaline in isolated median eminence: lack of negative feedback modulation.
A low volume (tissue holder, 100 microliter; dead space, 300 microliter) perfusion system has been developed for measuring [3H]noradrenaline release from isolated median eminence, where supramaximal electrical field stimulation can be applied. In tissue preloaded with [3H]noradrenaline, the resting release (0.4-2% of the content) was enhanced by electrical stimulation (2-10-fold increase). That the released radioactivity in response to electrical stimulation is mainly due to release of [3H]noradrenaline was confirmed by high pressure liquid chromatography combined with radiochemical detection. Evidence has been obtained that of the stimulation-evoked release of radioactivity 70-80 percent originates from noradrenergic neurons, however, the release observed at rest was not affected by 6-hydroxydopamine pretreatment. 6-Hydroxydopamine pretreatment selectively reduced the concentration of noradrenaline of the median eminence without affecting its dopamine content. The release evoked by electrical stimulation was [Ca2+]- and tetrodotoxin-sensitive. 4-Aminopyridine enhanced both the resting and stimulation-evoked release. The ratio between the amount of [3H]noradrenaline released by two consecutive stimulation periods at 2 Hz (120 shocks) was constant, 0.94 +/- 0.08. In contrast with other noradrenergic axon terminals, the release of [3H]noradrenaline in the median eminence was not subject to negative feedback modulation, yohimbine and xylazine had no effect. This conclusion was substantiated by in vivo study showing that yohimbine, an alpha2-adrenoceptor antagonist enhanced the turnover rate of noradrenaline in the cortex but not in the median eminence. Since noradrenergic axon terminals in the median eminence do not make synaptic contact and the released noradrenaline does not modulate its own release via alpha2-adrenoceptors, it is an interesting anatomical arrangement: the modulatory alpha2-adrenoceptors are located exclusively on the terminals of the hormone-containing neurons.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004574:Electromagnetic Fields; D005246:Feedback; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D051381:Rats; D014991:Xylazine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000631:Aminopyridines; D006892:Hydroxydopamines; D014991:Xylazine; D015016:Yohimbine; D016627:Oxidopamine; D015761:4-Aminopyridine; D002118:Calcium; D009638:Norepinephrine