E. S. Vizi

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.

Effects of intracerebroventricular AF64A administration on cholinergic, serotoninergic and catecholaminergic circuitry in rat dorsal hippocampus

Five nmol ethylcholine mustard aziridinium ion, a potential cholinotoxin was administered bilaterally into the cerebral ventricles of male rats at coordinates A -1.5, L +/- 1.5 and V -4.0 mm. The dorsal hippocampi were processed for choline acetyltransferase, serotonin or tyrosine hydroxylase immunocytochemistry 7 days after the injection to determine the specificity of the effect of the drug. Intrinsic choline acetyltransferase positive cells were also found after treatment, while the overall staining of fibres decreased. No change was observed in staining for either serotonin or tyrosine hydroxylase. Using the electron microscope, degenerating nerve terminals, with recognizable synaptic specializations were encountered, most frequently in stratum oriens and occasionally, degenerated CA3 pyramidal cells were observed. These findings are consistent with the neurochemical data obtained in parallel experiments with the morphological study in which it was found that acetylcholine content of the hippocampus was reduced by 73.4% 7 days after ethylcholine mustard aziridinium ion treatment, while dopamine, noradrenaline and serotonin levels were unaffected. Furthermore, the morphological studies indicate that ethylcholine mustard aziridinium ion can exert selective effects on the cholinergic system of dorsal hippocampus without significantly altering its cytoarchitecture.

Relaxation of human isolated pulmonary arteries by prostacyclin (PGI2)

The effects of indomethacin (IND) and PGI2 on the tone of human isolated pulmonary arteries were studied. Baseline tone of the vessels was increased by IND, electric stimulation (ES), norepinephrine (NE), prostaglandin F2α (PDF2α) or K+-excess. This high tone was decreased by PGI2 in a concentration dependent manner. IC50 values (molar concentrations producing 50% relaxation) for PGI2 were in the same concentration range (10 to 58.8 nmoles/l). The potency of the relaxant effect of PGI2 was inversely related to the magnitude of tone induced prior to the addition of PGI2 and independent of the type of tone inducer. It is suggested that the relaxant effect of prostacyclin on human pulmonary artery may be of clinical importance in the treatment of conditions associated with a rise in pulmonary vascular resistance.