Effects of clonidine on the stimulation-evoked release of3H-noradrenaline from superfused rat brain slices as a function of the biophase concentration

The influence of clonidine on the stimulation-evoked overflow of tritium was studied in brain slices preincubated with 3H-noradrenaline. The slices were prepared from parietal cortex (Cx), nucleus anterior hypothalami (nah) and nucleus tractus solitarii (nts). After preincubation, the tissues were superfused at 23 degrees C or 37 degrees C with a medium containing the noradrenaline uptake inhibitor desipramine. Electrical field stimulation was applied using stimulation frequencies of 0.3-10 Hz. At 23 degrees C/0.3 Hz, clonidine concentration-dependently inhibited the evoked overflow of tritium in all three brain regions. In contrast, at 23 degrees C/3 Hz the inhibitory effect of the drug in the Cx was abolished and a facilitation was observed in the nah and nts. When tested at increasing frequencies of stimulation in the nts at 23 degrees C, clonidine exerted a dual action, characterized by a reduction of electrically evoked responses at frequencies below 1 Hz and a facilitation at frequencies above 1 Hz. At 37 degrees C, clonidine concentration-dependently decreased the evoked overflow in all brain regions studied, this effect being more pronounced at 0.3 Hz than at 3 Hz. The apparent lack of an effect of clonidine on the stimulation-evoked overflow of tritium in the Cx at 23 degrees C/3 Hz was turned to a facilitation when noradrenaline (0.01 mumol/l) was included in the superfusion medium. Conversely, an inhibitory effect of clonidine was seen when the uptake blocker desipramine (as well as noradrenaline) was omitted from the superfusion medium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noradrenaline uptake inhibitors do not reduce the presynaptic action of clonidine on 3H-noradrenaline release in superfused synaptosomes

Summary The interaction between clonidine, as an agonist at the ₂-autoreceptors regulating noradrenaline release, and inhibitors of noradrenaline neuronal uptake was investigated in superfused synaptosomes, i.e. in conditions preventing accumulation of the released transmitter in the vicinity of presynaptic autoreceptors. Desipramine or cocaine did not decrease the inhibitory action of clonidine on the release of ³H-noradrenaline evoked by 15 mM KCl from rat cortex synaptosomes, even when the concentration ratio between uptake inhibitor and clonidine was very high. The present results do not support either the hypothesis of an interaction between imidazolines and noradrenaline uptake inhibitors at the level of ₂-autoreceptors, or that of a functional coupling between presynaptic ₂-autoreceptors and noradrenaline uptake mechanism.     

Facilitation by GABA of the potassium-evoked release of 3H-noradrenaline from the rat occipital cortex

Summary The effects of GABA were studied on the release of ³H-noradrenaline (³H-NA) evoked by potassium or by tyramine from slices of the rat occipital cortex and on the release of ³H-NA elicited by nerve stimulation from the cat nictitating membrane.GABA (30–1000M) facilitated the potassium-evoked release of ³H-NA in a concentration dependent manner. This facilitatory effect was not antagonized by bicuculline (1–100 M) or by picrotoxin (1–100 M). Exposure to the GABA agonist muscimol (1–100 M) did not affect either the spontaneous or the potassium-evoked release of ³H-NA.The facilitatory effect of GABA on the release of ³H-NA elicited by potassium was observed when the occipital cortex slices were exposed to 20 mM K⁺ during 1 min. When depolarization was induced by 35 mM K⁺ exposure to GABA failed to enhance the release of the neurotransmitter. GABA 300 M did not affect the release of the labelled neurotransmitter evoked by exposure to tyramine 0.6 M.In the cat nictitating membrane prelabelled with ³H-NA, the stimulation evoked release of the labelled neurotransmitter was not affected by GABA (10–300 M).In conclusion, GABA has a facilitatory effect on the calcium-dependent, potassium evoked release of ³H-NA when the depolarization is of moderate degree. This effect of GABA appears to be selective for the central nervous system.Some of the findings described in this paper have been presented at the Meeting of the British Pharmacological Society (March, 1978, Guildford, U.K.)     

B-HT 920, B-HT 933, and B-HT 958: presynaptic effects on electrically evoked 3H-noradrenaline release from slices of rat brain cortex and hypothalamus

Summary The effects of the three azepine compounds, B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]azepine), B-HT 933 [2-amino-6-ethyl-5, 6, 7, 8-tetrahydro-4H-oxazolo [4,5-d]azepine; azepexole] and B-HT 958 (2-amino-6-(p-chloro-benzyl)-4H-5, 6, 7, 8-tetrahydrothiazolo[5,4-d]azepine) on electrically evoked overflow of ³H-noradrenaline were studied. Slices from parietal cortex (C) or nucleus anterior hypothalami (nah) were incubated with ³H-noradrenaline, superfused at 23°C or 37°C in the presence of the noradrenaline uptake inhibitor desipramine (3 mol/l) and field stimulated at frequencies of 0.3 or 3 Hz. 1. At 37°C/0.3 Hz, B-HT 920 and B-HT 933 concentration-dependently decreased the evoked overflow of tritium in both regions studied, whereas B-HT 958 had no effect. 2. In a second set of experiments each drug was tested under three additional experimental conditions, i. e. 37°C/3 Hz, 23°C/ 0.3 Hz and 23°C/3 Hz. Increasing the stimulation frequency to 3 Hz or lowering the superfusion temperature to 23°C reduced the effects of B-HT 920 (1 mol/l) and B-HT 933 (10 mol/l) as compared to the effects at 37°C/0.3 Hz. When tested at 23°C/3 Hz, both drugs did not significantly affect the evoked overflow of tritium in the Cx or the nah. In contrast, B-HT 958 (10 mol/l), caused a facilitation of evoked overflow in both regions when the higher stimulation frequency or the lower superfusion temperature was used. Its release-enhancing action was most pronounced at 23°C/3 Hz. 3. Idazoxan (0.1 mol/l) antagonized the effects of BHT 920 (10 mol/l) and B-HT 933 (10 gmmol/l) in the Cx at 37°C/0.3 Hz. The ineffectiveness of B-HT 958 under these experimental conditions was not changed in the presence of idazoxan. Sulpiride (10 mol/l) did not affect the action of any of the three compounds. 4. From the patterns of effects obtained under the different experimental conditions it is concluded that B-HT 920 and B-HT 933 act as agonists at prejunctional ₂-adrenoceptors, whereas B-HT 958 acts as a weak antagonist at these sites. Send offprint requests to E. A. Singer at the above addressPreliminary results were presented at the 27th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, March 11–14, 1986, Mainz, Federal Republic of Germany     

Alpha-receptor-mediated modulation of 3H-noradrenaline release from rat brain cortex synaptosomes

Summary The effects of oxymetazoline and noradrenaline (in the presence of desipramine) on the release of ³H-noradrenaline from rat brain cortex synaptosomes were studied using a superfusion technique. Both drugs (at 1M concentrations) were found to reduce the depolarization-induced (15 mM K⁺) release of ³H-noradrenaline. The release-modulating effect of noradrenaline was antagonized by phentolamine and yohimbine.The data provide direct evidence for the hypothesis that -receptors modulating the release of noradrenaline are localized on varicosities of central noradrenergic neurones.     

3H-noradrenaline and 3H-5-hydroxytryptamine release from rat brain slices and its presynaptic alpha-adrenergic modulation after long-term desipramine pretreatment

Summary The electrically-evoked release of ³H-noradrenaline from superfused cortex and hippocampus slices was strongly enhanced (by about 50%) after long-term (4 weeks) pretreatment with desipramine (10 mg/kg, twice daily). The release-enhancing effect of the -receptor antagonist phentolamine was significantly reduced but the inhibitory effects of exogenous noradrenaline and clonidine on ³H-noradrenaline release were virtually unchanged after chronic desipramine treatment.The K⁺-induced release of ³H-noradrenaline from superfused synaptosomes obtained from rats pretreated with desipramine was about 25% higher than that from synaptomes of control animals. However, noradrenaline inhibited the K⁺-induced synaptosomal ³H-noradrenaline release to the same extent (viz. by about 55%) in both cases.The release of ³H-5-hydroxytryptamine induced by 26 mM K⁺ from cortex and hippocampus slices was not affected by chronic pretreatment with desipramine. In addition, no change was observed in the inhibitory effect of noradrenaline on ³H-5-hydroxytryptamine release.It is concluded that long-term pretreatment with desipramine leads to selective changes in the basic mechanism(s) of noradrenaline release rather than to changes in the sensitivity of presynaptic -adrenoceptors.     

Mechanism of nicotine-evoked release of 3H-noradrenaline in human cerebral cortex slices

1. The mechanism of stimulation of noradrenaline (NA) release by nicotine (NIC) was investigated in human cerebral cortex slices preloaded with 3H-noradrenaline. 2 NIC (10-1000 micro M) increased 3H-NA release in a concentration-dependent manner. 3. NIC (100 micro M)-evoked 3H-NA release was largely dependent on external Ca2+, and was attenuated by omega-conotoxin GVIA (0.1 micro M) but not by nitrendipine (1 micro M). 4. Tetrodotoxin (1 micro M) and nisoxetine (0.1 micro M) attenuated the NIC (100 micro M)-evoked release of 3H-NA. 5. Mecamylamine (10 micro M), dihydro-beta-erythroidine (10 micro M) and d-tubocurarine (30 micro M), but not alpha-bungarotoxin (alpha-BTX, 0.1 micro M), attenuated the NIC (100 micro M)-evoked release of 3H-NA. 6. NIC (100 micro M)-evoked release of 3H-NA was not affected by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 micro M) and D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 100 micro M), but attenuated by MK-801 (10 micro M). MK-801 (0.1-1000 micro M) displaced the specific binding of 3H-nisoxetine with K(i) values of 91.2 micro M. NIC (100, 300 and 1000 micro M) did not induce 3H-D-aspartate release in human cerebral cortex slices. 7. NIC (100 micro M)-evoked release of 3H-NA was attenuated by 7-nitroindazole (10 micro M), N(G)-nitro-L-arginine methyl ester HCl (L-NAME, 30 micro M), N(G)-monomethyl-L-arginine acetate (L-NMMA, 300 micro M). [(3)H]-NA release induced by NIC (100 micro M) was attenuated by methylene blue (3 micro M) and 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ, 10 micro M), and enhanced by zaprinast (30 micro M). 8. In conclusion, NIC stimulates the release of 3H-NA through activation of alpha-BTX-insensitive nicotinic acetylcholine receptors in the human cerebral cortex slices and this action of NIC is associated with modulation of the NO/cGMP pathway.     

Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex

The effects of adenosine and some related purines on the K+-induced release of 3H-noradrenaline from rat cerebral cortex slices were determined in a superfusion system. Adenosine and ATP caused a dose-dependent inhibition of 3H-NA release with a maximal effect of 35% at 10(-4) M. Theophylline, 10(-4) M, antagonized the inhibitory effect of adenosine. The results support the hypothesis that at least some of the central stimulant effects of the methylxanthines could be related to blockade of a purinergic inhibitory tone on noradrenergic synaptic output.     

Presynaptic action of adrenaline on adrenoceptors modulating stimulation-evoked 3H-noradrenaline release from rabbit isolated aorta

Summary The purpose of this investigation was to study the effect of adrenaline on presynaptic adrenoceptors by recording the release of ³H-noradrenaline evoked by electrical-field stimulation. Adrenaline (10^–10–³ × 10^–9 mol/l) had no effect on the ³H-overflow evoked by stimulation of aorta preloaded with ³H-noradrenaline. At 10^–8 and 3 × 10^–8 mol/l, the ³H-overflow was decreased by up to 47%. The maximum decrease was more marked in the presence of either cocaine (3 × 10^–5 mol/l) plus corticosterone (4 × 10^–5 mol/l), cocaine (3.3 × 10^–6 mol/l) plus normetanephrine (4 × 10^–5 mol/l), or desipramine (10^–6 mol/l) plus normetanephrine (10^–5 mol/l). The relationship between adrenaline-induced decrease and stimulation-frequency was dependent on the experimental design: either the decrease was the same at all frequencies (1–16 Hz) or it was more marked, the lower the frequency (1 > 3 > 8 Hz). Phentolamine and rauwolscine (both 10^–6 mol/l) antagonized the inhibitory effect of adrenaline (10 ^{– 8}–10^–6 mol/l). Phenoxybenzamine (10^–6 mol/l), prevented the inhibitory effect. No enhancing effect of adrenaline (10^–9–10^–6 mol/l) was observed in the presence of these three -adrenoceptor antagonists. Our results suggest that adrenaline activates inhibitory ₂-adrenoceptors, but not facilitatory -adrenoceptors on postganglionic sympathetic nerve terminals in rabbit aorta. Send offprint requests to J. Abrahamsen at the above address     

Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices

Summary The effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and -acetylenic GABA and gabaculine, both y-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was ₁- Ca²⁺-dependent stimulus-evoked release of endogenous aspartate. AOAA (10^–4 and 10^–3 M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 × 10^–5 M), -acetylenic GABA (10^-4 M) and gabaculine (10^-5 M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced ₁- decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata Send offprint requests to T. Kubo at the above address     

Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors

Summary The effects of histamine and related drugs on the evoked tritium overflow from superfused rat brain cortex slices preincubated with³H-noradrenaline were determined. Tritium overflow was stimulated electrically (3 Hz; slices superfused with normal physiological salt solution) or by introduction of CaCl₂ 1.3 mmol/l (slices superfused with Ca²⁺-free medium containing K⁺ 20 mmol/l).Histamine slightly decreased the electrically evoked^H overflow in slices superfused in the presence of desipramine. The degree of inhibition obtained with histamine was doubled when both desipramine and phentolamine were present in the superfusion medium (pIC₁₅ 6.46). Under the latter condition, the evoked overflow was inhibited by the H₃ receptor agonist R-(–)--methylhistamine and its S-(+) enantiomer (pIC₁₅ 7.36 and 5.09, respectively), but was not affected by the H₂ receptor agonist dimaprit and the H₁ receptoragonist 2-thiazolylethylamine (both at up to 32 µmol/l). The concentration-response curve of histamine was shifted to the right by the H3 receptor antagonists thioperamide, impromidine and burimamide (apparent pA₂ 8.37, 6.86 and 7.05, respectively), by the H₂ receptor antagonist ranitidine (apparent pA₂ 4.27) and was not affected by the H₁ receptor antagonist dimetindene (32 µmol/l). The inhibitory effect of R-(–)--methylhistamine on the evoked overflow was also counteracted by thioperamide. Given alone, none of the five histamine receptor antagonists affected the evoked overflow. In the absence of desipramine plus phentolamine, impromidine and burimamide facilitated the electrically evoked³H overflow whereas thioperamide had no effect. The facilitatory effects of impromidine and burimamide were abolished by phentolamine, but not affected by desipramine. The concentration-response curve of noradrenaline for its inhibitory effect on the evoked overflow was shifted to the right by impromidine and burimamide, but not influenced by thioperamide (apparent pA₂ 5.24, 5.04 and <6.5, respectively; experiments carried out in the presence of desipramine). In slices superfused with Ca²⁺-free K⁺-rich medium containing tetrodotoxin, desipramine plus phentolamine, the tritium overflow evoked by introduction of Ca²⁺ was inhibited by histamine; the concentration-response curve of histamine was shifted to the right by thioperamide.The present study shows that the inhibitory effect of histamine on noradrenaline release in the rat brain cortex involves presynaptic H₃ receptors and that the degree of inhibition is increased in the presence of phentolamine. The H₃ receptor antagonists impromidine and burimamide are weak ₂-adrenoceptor antagonists. Send offprint requests to E. Schlicker at the above address     

On the mechanism of alpha-receptor mediated modulation of 3H-noradrenaline release from slices of rat brain neocortex

Summary Brain cortical slices were superfused with Krebs-Ringer media and the effects of oxymetazoline (an -adrenoceptor agonist) and phentolamine (an -antagonist) on depolarization-induced ³H-NA release were examined. Depolarization was effected by various K⁺-concentrations or by electrical pulses.The effects of the -receptor agents on stimulated ³H-NA overflow appeared to be dependent on the strength of the depolarizing stimulus. Thus, at low K⁺-concentrations (13 or 26 mM) oxymetazoline decreased and phentolamine increased the stimulated overflow, while at 56 mM K⁺ little or no modulation was found. The agents acting on -receptors modulated ³H-NA release in a dose-dependent way (5 · 10^–8–10^–5 M).The lack of modulation by oxymetazoline of ³H-NA release induced by 56 mM K⁺ seems not to be due to a high concentration of NA released into the synaptic cleft, since reduction of the endogenous NA level by pretreatment with -methyl-para-tyrosine did not reveal such modulation.However, oxymetazoline was found to decrease 56 mM K⁺-induced ³H-NA release effectively, if the Ca²⁺-concentration in the medium was lowered from 1.2 to 0.2 mM. This suggests that -receptor mediated modulation of release may occur as a result of a change in Ca²⁺-availability to the depolarization-secretion process. In addition, hyperpolarization of nerve endings might be involved in the modulatory process, as concluded from calculations of the (theoretical) trans-membrane potential at various K⁺-concentrations.Although the -receptors modulating NA release seem to be localized presynaptically, their precise location remains uncertain. Experiments with tetrodotoxin suggested that the -receptor mediated modulation does not operate via a local interneuronal loop.     

Baclofen and phaclofen modulate GABA release from slices of rat cerebral cortex and spinal cord but not from retina.

1. The effects of (-)-baclofen, muscimol and phaclofen on endogenous gamma-aminobutyric acid (GABA) release from rat cortical slices, spinal cord slices and entire retinas were studied. 2. The spontaneous resting release of GABA from the three tissues was 3 to 6 pmol mg-1 wet wt 10 min-1. Depolarization of cortical slices with KCl (50 mM) (high-K) produced an 8 fold increase in GABA release but high-K did not evoke an increased release of GABA from spinal slices or retinas. 3. When rats were injected with gamma-vinyl-GABA (250 mg kg-1 i.p.) (GVG) 18 h before death, the tissue GABA stores were increased 3 to 6 fold and high-K then evoked striking Ca-dependent releases of GABA from all three tissues. Thus, in subsequent experiments, unless otherwise stated, the nervous tissues were taken from GVG-treated rats. 4. (-)-Baclofen (10 microM) significantly reduced the K-evoked release of GABA from cortical and spinal slices but retinal release was not affected, even at a concentration of (+/-)-baclofen of 1 mM. For cortical slices, the IC50 for baclofen was approximately 5.2 microM. The inhibitory effect of baclofen on GABA release from cortical slices also occurred in slices prepared from saline-injected rats, indicating that GVG treatment did not qualitatively affect the results. 5. The inhibitory effect of (-)-baclofen on the K-evoked release of GABA from cortical and spinal slices was antagonised by phaclofen (500 microM), confirming that baclofen was producing its effects by acting at the GABAB-receptor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of 3-acetylpyridine on serotonin uptake and release from rat cerebellar slices.

The cerebellum receives indolaminergic fibers influencing Purkinje cell discharges. Data from our laboratories have demonstrated an endogenous release of serotonin (5-HT) and a Na(+)-dependent uptake and Ca(2+)-dependent release of [3H]5-HT from slices, homogenates and synaptosomal fractions of the rat cerebellar molecular layer. While the neurotransmitter produced by climbing fibers has been sought for in several studies and some of the classical transmitters have been ruled out, as yet this neurotransmitter is unknown. The aim of this work was to measure the 5-HT uptake and release from rat cerebellar slices, 6 h and 15 days after intraperitoneal injection of 3-acetylpyridine (3-AP) (75 mg/kg), harmaline (15 mg/kg) and nicotinamide (300 mg/kg). A histological study of medulla and cerebellar cortex in these animals showed destruction of neurons in the inferior olivary nuclei and changes in the granulation of the cortical molecular layer in the cerebellum. A significant reduction of the 5-HT content (100%), 5-HT uptake (60%) and its Vmax (60%) was seen on the 5th day, in cerebellar preparations obtained from rats injected with 3-AP. The Ca(2+)-dependent release of 5-HT from these preparations was found to be similar to the basal values, in spite of depolarizing stimuli with 53 mM KCl or veratrine (60 micrograms/ml). The results suggest that 5-HT could play an important role as neurotransmitter produced by some climbing fibers.     

Release of 3H-5-hydroxytryptamine by amiflamine and related phenylalkylamines from rat occipital cortex slices

Summary In the present study Amflamine and other related reversible monoamine oxidase-A (MAO-A) inhibitory phenylalkylamines were examined in vitro for their ability to induce release of ³H-5-hydroxytryptamine (³H-5-HT) from rat occipital cortex slices. The slices were preincubated with ³H-5-HT 0.1 mol/l in the presence of the irreversible MAO inhibitor pargyline 50 mol/l and then continuously superfused. The effects were compared with those of the 5-HT releaser p-chloroamphetamine (pCA), the reversible MAO-inhibitor -ethyltryptamine and the 5-HT uptake inhibitor citalopram. Amiflamine, some related compounds and -ethyltryptamine which in vivo after transport by the 5-HT uptake mechanism preferentially inhibit MAO within the serotonergic neurons caused a Cat²⁺-independent release of ³H-5-HT. Some transported compounds, particularly NBF 027 were, however, very weak releasers of 5-HT. This release and that induced by pCA was prevented by citalopram in the superfusion medium. FLA 365, FLA 417 and FLA 1088, which are not transported into the neurons, were poor releasers of 5-HT. It is concluded that compounds which were effective releasers of 5-HT in vitro were those that are transported into the serotonergic neurons by the 5-HT carrier in vivo and has in addition an ability to mobilise vesicular 5-HT. Send offprint requests to A.-L. Ask at the above address     

Lack of presynaptic modulation by isoprenaline of 3H-noradrenaline release from rabbit isolated ear artery

Summary The aim of the present investigation was to examine whether or not presynaptic facilitatory -adrenoceptors are detectable on the postganglionic nerves in the rabbit isolated ear artery. Strips of rabbit central ear artery were incubated with ³H-noradrenaline (10^–7 mol/l; 30 min or 10^–6 mol/l; 60 min). Subsequently, they were washed repeatedly with physiological salt solution. The strips were subjected to electrical-field stimulation (S₁–S₈) and the resultant ³H-overflow was determined.When the ear artery was stimulated with 150 pulses (0.5 ms; 3 Hz; 225 mA), isoprenaline (10^–9–10^–6 mol/l) either alone or in the presence of either rauwolscine (10^–6 mol/l) or phentolamine (10^–6 mol/l) did not alter the stimulation-evoked ³H-overflow. This was also the case in the presence of rauwolscine (10^–6 mol/l) plus either the selective phosphodiesterase inhibitor ICI 63 197 (3 × 10^–5 mol/l) or forskolin (10^–6 mol/l). When the ear artery was stimulated with 300 pulses (1 ms; 5 Hz; 225 mA), isoprenaline had no effect on the stimulation-evoked ³H-overflow. This was also the case when phentolamine (10^–6 mol/l) was present. Propranolol (10^–7–10^–5 mol/l) did not alter the stimulation-evoked ³H-overflow. In some experiments, the stimulation current was reduced to 175 mA in order to obtain similar reference release (S₃) values despite the presence of rauwolscine (150 pulses; 0.5 ms; 3 Hz). Even then, isoprenaline (10^–9–10^–6 mol/l) did not change stimulation-evoked ³H-overflow. The results suggest that postganglionic sympathetic nerves in rabbit central ear artery do not possess presynaptic facilitatory -adrenoceptors. Send offprint requests to J. Abrahamsen at the above address     

Effect of metavanadate on the uptake and release of noradrenaline in rat brain cerebral cortex slices

The effect of vanadium (as VO3-) on the uptake and release of tritiated noradrenaline ([3H]NA) was studied in vitro in rat cerebral cortex slices. Vanadate inhibited [3H]NA uptake and the inhibition was dependent upon concentration and on incubation time. The IC50 value (20 min incubation) was 8 X 10(-5) M of vanadate. Inhibition of Na+, K+ -ATPase activity by VO3-, chelation of noradrenaline or autooxidation of catecholamine by this oxyanion might contribute to the decrease of [3H]NA uptake. Vanadate inhibited also the release of [3H]NA in a time- and concentration-dependent fashion.