Nitric oxide modulates the release of serotonin in the rat hypothalamus

To investigate the effect of nitric oxide (NO) on the release of serotonin and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA), the posterior hypothalamus of the conscious rat was superfused through a push-pull cannula with drugs which either liberate NO, or inhibit NO synthase (NOS). The NO donors, linsidomine, diethylamine/nitric oxide (DEA/NO), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-glutathione (SNOG) and sodium nitroprusside influenced the release of serotonin in a biphasic way. Low concentrations of drugs diminished, while higher concentrations of these compounds enhanced the outflow of serotonin. The NOS inhibitors N(G)-methyl-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NINA) enhanced the serotonin release. A high concentration of L-NAME slightly diminished the outflow of serotonin. Inhibition of the guanylyl cyclase by oxodiazolo[4, 3]quinoxaline-one (ODQ) abolished the changes in serotonin outflow induced by both low and high concentrations of linsidomine. The extracellular concentration of the 5-HIAA was not influenced by the compounds used. These data suggest that endogenous NO modulates the release of serotonin in a biphasic and cGMP-dependent way.     

7-Nitroindazole, nNOS inhibitor, attenuates amphetamine-induced amino acid release and nitric oxide generation but not lipid peroxidation in the rat brain

Summary. The aim of the present study was to elucidate whether amphetamine modulates the output of the neurotransmitters glutamate, aspartate, GABA and acetylcholine (ACh) in nucleus accumbens (NAc) as well as the formation of lipid peroxidation (LPO) and nitric oxide (NO). D,L-amphetamine (AMPH, 5mg/kg, i.p., 4 times every 2h) was injected into anaesthetized rats and the release of neurotransmitters in the NAc, tissue content of NO and LPO products were determined.While AMPH increased the release of aspartate, GABA and ACh in the NAc, the glutamate release was not affected. Levels of NO and LPO products were elevated in striatum and cortex. Pretreatment with the neuronal NO synthase inhibitor 7-nitroindazole (50mg/kg, i.p.) was highly effective in abating the rise of the neurotransmitter release and NO generation but failed to influence the intensity of LPO elicited by the AMPH administration.These findings suggest that activation of NO synthesis is a potent factor in the AMPH-induced neurotransmitter release and that activation of NO synthesis and LPO by AMPH are not parallel processes.     

动脉血压改变对大鼠下丘脑后部GABA释放的影响

用推～挽灌流技术，定位灌流大鼠下丘脑后部，同时ｉｖ给予去氧肾上腺素（１５μｇ·ｋｇ·ｍｉｎ－１）和静脉输血（３ｍｌ／１００ｇ，ｗｔ）引起血压升高时，下丘脑后部γ－氨基丁酸（ＧＡＢＡ）的释放率增加，而ｉｖ给予硝普钠、氯化四氯吲哚铵和控制性失血导致血压下降时，ＧＡＢＡ的释放率减少。进一步证明下丘脑ＧＡＢＡ能神经系统参与外周动脉血压的调节，且有降压作用。     

Effects of adrenergic drugs on pressor responses to hypothalamic stimulation

Summary In 12 female dogs renal excretion and catabolism of ¹⁴C-(±)-adrenaline, ¹⁴C-(±)-noradrenaline, ¹⁴C-dopamine and ³H-(±)-normetanephrine were investigated using a modified stop-flow technique. Radioactive compounds were infused, together with inulin, into the left renal artery for 10 min. During the first 2 min of the infusion period the left ureter was occluded. Urine samples were serially collected from both kidneys up to the end of the infusion. In the urine the total radioactivity and the pattern of radioactive metabolites were measured.On average, the infused kidney excreted from the infused dose of ¹⁴C-adrenaline 9.4% as adrenaline, 27.9% as metanephrine and 5.8% as deaminated or conjugated metabolites. From infused ¹⁴C-noradrenaline 7.4% was excreted as noradrenaline, 3.5% as normetanephrine and 1% as deaminated or conjugated compounds. When ³H-normetanephrine was infused the urine contained only radioactive normetanephrine (22.2%). From the infused dose of ¹⁴C-dopamine 9.6% was excreted as dopamine, 16.2% as 3-O-methyldopamine and 3.7% as deaminated or conjugated compounds. — Urine from the other kidney contained 1/25 to 1/5 the radioactivity of that from the infused side, but the pattern of radioactive compounds was similar.From the excretion rate of simultaneously infused inulin the filtration fraction of the infused kidney was determined. That part of the infused ¹⁴C-catecholamines which was excreted unmetabolized in the urine, corresponds to the filtration fraction in this kidney. Therefore, it is suggested, that in mammals the unmetabolized catecholamines of the urine are mainly excreted by glomerular filtration and not by tubular secretion. On the other hand, the urinary O-methylated radioactive catecholamines, which were excreted by the infused kidney at a high rate, were formed in this organ from the infused catecholamines and were excreted by tubular secretion. Thus, in mammals tubular secretion is linked to an inactivation of these compounds by O-methylation.Supported by the Deutsche Forschungsgemeinschaft.     

Untersuchungen zur Bedeutung einer ATPase aus Milznervengranula

Ohne Zusammenfassung     

ATP-, ADP-, Pyruvat- und Lactatgehalt in Blut und Leber nach intravenöser Fructose- und Mannosebelastung

Ohne ZusammenfassungMit 3 TextabbildungenDurchgeführt mit finanzieller Unterstützung und unter Verwendung apparativer Leihgaben der Deutschen Forschungsgemeinschaft.Auszugsweise am 5. 2. 1960 in Gießen vorgetragen, Schriftreihe des Instituts für Ernährungswissenschaften der Universität Gießen, Bd. 2, S. 57, 1960.Physiologisches Institut der Universität Athen, Stipendiat der Humboldt-Stiftung.     

Nitric oxide as modulator of neuronal function

The gas NO is a messenger that modulates neuronal function. The use of NO donors and NO synthase inhibitors as pharmacological tools revealed that this free radical is probably implicated in the regulation of excitability and firing, in long-term potentiation and long-term depression, as well as in memory processes. Moreover, NO modulates neurotransmitter release. In vivo and in vitro studies have shown that, in all brain structures investigated, endogenous NO modulates the release of several neurotransmitters, such as acetylcholine, catecholamines, excitatory and inhibitory amino acids, serotonin, histamine, and adenosine. In most cases, enhanced NO level in the tissue increases the release of neurotransmitters, although decreasing effects have also been observed. Cyclic 3'-5' guanosine monophosphate and glutamate mediate the modulation of transmitter release by NO. Recent observations suggest that the release of some transmitters is dually influenced by NO. Thus, besides modulation by presynaptically located auto- and heteroreceptors, NO released from nitrergic neurons seems to play a universal role in modulating the release of transmitters in the brain.     

Release of endogenous histamine in the hypothalamus of anaesthetized cats and conscious,freely moving rabbits

Summary The hypothalamus of anaesthetized cats and conscious, freely moving rabbits was superfused with CSF through double-walled, push-pull cannulae and the release of endogenous histamine was determined in the superfusates by a radioenzymatic assay.In the posterior hypothalamic area of the anaesthetized cat, the rate of release of endogenous histamine varied rhythmically; phases of high rate of release appeared at 60 min cycles. The release of histamine was increased by electrical stimulation of the superfused area, as well as by hypothalamic superfusion with potassium-rich CSF.In the conscious rabbit, the anterior hypothalamic area and the posterior hypothalamic nucleus were superfused simultaneously. In both regions, the resting release of histamine varied rhythmically at approximately 70 min cycles. Phases of high or low-rate of release in the anterior hypothalamic area coincided with the corresponding phases in the posterior hypothalamic nucleus.The rhythmic release of endogenous histamine in the hypothalamus, as well as the ability of depolarizing stimuli to enhance the release of the amine support the idea that histamine acts as a neurotransmitter in the central nervous system.This work was supported by the Deutsche ForschungsgemeinschaftPart of the results has been presented at the International Histamine Symposium, Okayama, July 1981