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H Prast

Publications and source records attributed to H Prast.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nitric oxide-induced release of acetylcholine in the nucleus accumbens: role of cyclic GMP, glutamate, and GABA.

We have previously shown that the basal acetylcholine release in the ventral striatum is under the enhancing influence of endogenous nitric oxide (NO) and that NO donors cause pronounced increases in the acetylcholine release rate. To investigate the role of cyclic GMP, glutamate, and GABA in the NO-induced acetylcholine release, we superfused the nucleus accumbens, (Nac) of the anesthetized rat with various compounds through a push-pull cannula and determined the neurotransmitter released in the perfusate. Superfusion of the Nac with the NO donors diethylamine/NO (DEANO; 100 micromol/L), S-nitroso-N-acetylpenicillamine (SNAP; 200 micromol/L), or 3-morpholinosydnonimine (SIN-1; 200 micromol/L) enhanced the acetylcholine release rate. The guanylyl cyclase inhibitor 1H-(1,2,4)-oxodiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L) abolished the effects of DEANO and SIN-1. 6-(Phenylamino)-5,8-quinolinedione (LY-83583; 100 micromol/L), which also inhibits cyclic GMP synthesis, inhibited the releasing effects of DEANO and of SNAP, whereas the effect of SIN-1 on acetylcholine release was not influenced. The DEANO-induced release of acetylcholine was also abolished in the presence of 20 micromol/L 6,6-dinitroquinoxaline-2,3-dione (DNQX) and 10 micromol/L (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Simultaneous superfusion with 50 micromol/L quinpirole and 10 micromol/L 7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83566) was ineffective. Superfusion with 500 micromol/L DEANO decreased the release of acetylcholine. The inhibitory effect of 500 micromol/L DEANO was reversed to an enhanced release on superfusion with 20 micromol/L bicuculline. Bicuculline also enhanced the basal release rate. These findings indicate that cyclic GMP mediates the NO-induced release of acetylcholine by enhancing the outflow of glutamate. Dopamine is not involved in this process. Only high concentrations of NO increase the output of GABA, which in turn decreases acetylcholine release. Our results suggest that cells that are able to release glutamate, such as glutamatergic neurons, are the main target of NO in the Nac.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Similar deficits of central histaminergic system in patients with Down syndrome and Alzheimer disease.

In order to study whether Alzheimer-like neuropathological changes involve the central histaminergic system we measured the concentration of histamine, its precursor histidine as well as the activity of histidine decarboxylase (HDC) and histamine-N-methyl-transferase (HMT) in frontal cortex of aging Down syndrome (DS) patients, Alzheimer patients and control individuals. The study populations were also investigated for choline acetyltransferase (ChAT) activity, since reduced ChAT activity is an established biochemical hallmark in DS and Alzheimer disease (AD). HDC and ChAT activity were reduced in brains of both DS and Alzheimer patients versus control patients. Additionally, we observed a significant decrease of histamine levels in the DS group. Histamine levels in AD brains tended to be decreased. Histidine concentrations and HMT activities were comparable between the three groups. Thus, our results for the first time show histaminergic deficits in brains of patients with DS resembling the neurochemical pattern in AD. Neuropathological changes may be responsible for similar neurochemical alterations of the histaminergic system in both dementing disorders.

Aged↗
PubMed1997

The ultradian EEG rhythm coincides temporally with the ultradian rhythm of histamine release in the posterior hypothalamus.

In the posterior hypothalamus of the rat, EEG power and release rates of several neurotransmitters oscillate according to ultradian rhythms. To investigate whether a causal relationship exists between EEG power and histamine release, the posterior hypothalamic area of the anaesthetized rat was superfused through a push-pull cannula combined with a tungsten electrode. Simultaneous EEG recording and determination of histamine release revealed that ultradian rhythms in the delta and theta frequency bands are negatively correlated to the release rate of histamine; periods of high neuronal activity, which might reflect synchronization of firing, coincide temporally with low release rate of histamine, while periods of low neuronal activity coincide with high histamine release rate. The alpha and beta frequency bands did not correlate with histamine release. The ultradian rhythm of EEG power and histamine release might be of importance for regulatory mechanisms, such as the secretion of hormones.

Activity Cycles↗
PubMed1996

Histaminergic neurons facilitate social memory in rats.

The social memory test was used so as to investigate whether brain histamine is involved in short-term memory. Histamine injected intracerebroventricularly (i.c.v.) decreased investigation time of a juvenile rat by an adult rat. A similar effect was elicited by i.c.v. administration of histidine. Compared with the control animals, rat pretreatment with alpha-fluoromethylhistidine (FMH), which inhibits neuronal synthesis of histamine, prolonged recognition time. The H3-receptor agonist immepip also prolonged investigation time, while the H3-antagonist thioperamide exerted the opposite effect. Treatment with histidine increased, while treatment with FMH decreased histamine levels in various brain regions. It is concluded that histamine released from histaminergic neurons facilitates short-term memory.

Animals↗
PubMed1996

Influence of histamine receptor agonists and antagonists on ultradian rhythm of EEG in the posterior hypothalamus of the rat.

The delta and theta frequency bands of the electroencephalogram (EEG) in the posterior hypothalamic area (PH) of rats vary according to an ultradian rhythm with a frequency of approximately 1 cycle/100 min. The influence of histamine-related drugs on the ultradian hypothalamic EEG rhythm was now studied in urethane anaesthetized rats. Injected into the lateral ventricle, metoprine (inhibitor of histamine catabolism) and alpha-fluoromethylhistidine (inhibitor of histamine synthesis) did not alter the duration of the rhythmic changes. The H1 receptor agonist 2-(2-aminoethyl)-thiazole was ineffective, while mepyramine (H1 receptor antagonist) prolonged the cycle duration of delta and theta frequency bands. Stimulation of H2 and H3 receptors by amthamine and immepip, respectively, also prolonged the cycle duration of these frequency bands, while the H2 antagonist famotidine and the H3 antagonist thioperamide exerted the opposite effects. Our results indicate that the ultradian EEG rhythm in the PH is susceptible to regulatory influences mediated by the histaminergic system of the brain.

Activity Cycles↗
PubMed1996

Influence of mediobasal hypothalamic lesion and catecholamine receptor antagonists on ultradian rhythm of EEG in the posterior hypothalamus of the rat.

The delta and theta frequency bands of the EEG in the posterior hypothalamic area (PH) of the urethane-anaesthetized rat vary according to an ultradian rhythm with a frequency of approximately one cycle per 100 min. Injected into the lateral ventricle, prazosin (150 nmol) abolished the rhythmic changes, propranolol (150 nmol) increased, while yohimbine, SKF-83566 and sulpiride (150 nmol each) decreased the cycle duration. Electrocoagulation of the rostral arcuate nucleus and median eminence (Arc-ME) of medial basal hypothalamus abolished the rhythmic EEG changes in the PH. Our results indicate that the ultradian EEG rhythm in the PH is susceptible to regulatory influences mediated by noradrenergic and dopaminergic neurons. For the generation of the ultradian rhythm, the functional integrity of the Arc-ME is required.

Animals↗
PubMed1996

Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus.

To investigate the influence of nitric oxide (NO) on the release of histamine and glutamate, the anterior hypothalamus of anaesthetized rats was superfused through a push-pull cannula either with artificial cerebrospinal fluid (CSF) or with various drugs dissolved in CSF. Hypothalamic superfusion with the NO-donating compounds linsidomine (200 mumol/l) or diethylamine-NO (DEANO, 100 mumol/l) led to a pronounced and sustained decrease in the histamine release rate, whereas the release rate of glutamate was enhanced. Superfusion with the inhibitor of NO synthase L-NG-nitro-L-arginine methyl ester (L-NAME, 200 mumol/l) increased the histamine release rate. The inhibitory effect of 200 mumol/l linsidomine was abolished by atropine (10 mumol/l). Superfusion with the glutamate receptor agonists glutamate (100 mumol/l) or N-methyl-D-aspartate (NMDA, 50 mumol/l) enhanced the histamine release rate. In the presence of linsidomine, the releasing effect of NMDA was not changed. These findings demonstrate that the release of histamine in the hypothalamus is diminished by endogenous NO. This effect of NO on histamine release seems to be due to enhanced release of acetylcholine from vicinal cholinergic neurons via stimulation of muscarinic acetylcholine receptors located presynaptically on histaminergic neurons. The NO-induced glutamate release seems to exert a subordinate stimulatory effect on histamine release. Finally, the inhibition of histamine release by NO is not due to blockade of NMDA receptors.

Animals↗
PubMed1995

Ultradian rhythm in the delta and theta frequency bands of the EEG in the posterior hypothalamus of the rat.

The EEG signal of the area hypothalami posterior (PH) was recorded in the urethane anaesthetized rat. The main characteristic of the EEG in this brain region was intermittent oscillations of high amplitude in the delta and theta frequency bands. Oscillations of the alpha and beta frequency bands showed comparatively lower variations. Time distribution analysis of the EEG spectral power revealed that the delta and theta rhythms appeared and disappeared according to an ultradian rhythm with a frequency of approximately 1 cycle per 100 min. No significant rhythm was found in the alpha and beta band. The rhythm frequency of neuronal activity in the PH is very similar to the ultradian frequency of pulsatile neurotransmitter release in the PH demonstrated previously.

Activity Cycles↗
PubMed1995

Adenosine release in the ventral striatum of the rat is modulated by endogenous nitric oxide.

The influence of nitric oxide (NO) on adenosine release was investigated by the push-pull technique in the ventral striatum of the urethane-anaesthetized rat. Superfusion with the NO donor diethylamine-NO enhanced, whereas superfusion with the NO synthase inhibitor L-NG-nitroarginine methyl ester decreased the output of adenosine. The effect of L-NG-nitroarginine methyl ester was abolished by L-arginine methyl ester. These findings indicate that, in the ventral striatum of the rat, NO modulates adenosine release.

Adenosine↗
PubMed1995

Nitric oxide modulates the release of acetylcholine in the ventral striatum of the freely moving rat.

The influence of nitric oxide on acetylcholine release in the ventral striatum was investigated by the push-pull superfusion technique in the conscious, freely moving rat. Superfusion with the nitric oxide donors S-nitroso-N-acetylpenicillamine or with 3-morpholino-sydnonimine caused a pronounced increase in striatal acetylcholine release. This effect was prevented by superfusion with tetrodotoxin. Pre-superfusion with the guanylyl cyclase inhibitor methylene blue abolished the effect of 3-morpholino-sydnonimine. Superfusion of the ventral striatum with the guanylyl cyclase inhibitor LY83583 decreased acetylcholine release by 60% of basal release, whereas the less specific guanylyl cyclase inhibitor methylene blue was ineffective in this respect. Superfusion of the ventral striatum with inhibitors of nitric oxide synthase also led to different effects on basal acetylcholine release. Superfusion with L-NG-methylarginine did not influence basal acetylcholine release, whereas superfusion with L-NG-nitroarginine or with L-NG-nitroarginine methyl ester led to a substantial decrease in acetylcholine output, the latter compound being more effective. The effect of L-NG-nitroarginine was abolished by simultaneous superfusion with L-arginine. The effects of NO donors and of LY83583 suggest that NO increases acetylcholine release, probably by a cGMP-dependent mechanism. The effectiveness of nitric oxide synthase inhibitors shows that the activity of striatal neurons is under the permanent influence of nitric oxide, that leads, via a direct or indirect mechanism, to continuous enhancement of acetylcholine release. In conclusion, our findings suggest that NO synthesized in the ventral striatum acts as an intracellular messenger which modulates acetylcholine release.

Acetylcholine↗
PubMed1994

In vivo modulation of histamine release by autoreceptors and muscarinic acetylcholine receptors in the rat anterior hypothalamus.

The modulation of histamine release by histamine and muscarinic acetylcholine receptors was investigated by using the push-pull technique. The anterior hypothalamic area of the conscious, freely moving rat was superfused through the push-pull cannula with CSF or with CSF containing drugs and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with tetrodotoxin (10 mumol/l) led to a pronounced and sustained decrease in the histamine release rate. Superfusion with compound 48/80 (100 mg/l) was ineffective. Hypothalamic superfusion with the H3 agonist (R)-alpha-methylhistamine inhibited, while superfusion with the H3 antagonist thioperamide enhanced the release of histamine. The release of histamine was inhibited on hypothalamic superfusion with the muscarinic receptor agonists carbachol or oxotremorine. Histamine release was enhanced by atropine, and this release-enhancing effect was abolished by oxotremorine. The selective M1 antagonist pirenzepine (100 mumol/l) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10 mumol/l), which blocks M1 and M3 receptors, also enhanced the release rate of histamine. On the other hand, 50 and 100 mumol/l methoctramine (M2 receptor antagonist) 10 and 100 mumol/l p-fluoro-hexahydro-siladifenidol (p-F-HHSiD, a M3 receptor antagonist) were ineffective. It is concluded tht histamine released in the hypothalamus originates predominantly from neurons. The release of histamine is modulated by H3 autoreceptors. The histamine release is also modulated by cholinergic neurons which modify histamine release from histaminergic neurons by stimulating M1 muscarinic acetylcholine heteroreceptors probably located on histaminergic neurons.

Animals↗
PubMed1994

H3 autoreceptors and muscarinic acetylcholine receptors modulate histamine release in the anterior hypothalamus of freely moving rats.

To investigate the modulation of histamine release by autoreceptors and heteroreceptors, the rat anterior hypothalamus was superfused through a push-pull cannula with agonists or antagonists of histamine and acetylcholine muscarinic receptors. Superfusion with the H3 receptor agonist (R)-alpha-methylhistamine inhibited, while superfusion with thioperamide (H3 antagonist) enhanced histamine release. Superfusion with carbachol (a mixed M1, M2, M3 agonist) inhibited the release of histamine. The release of endogenous histamine was enhanced on superfusion with atropine (a mixed M1, M2, M3 antagonist). The M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine enhanced the release rate of histamine. It is concluded that in the anterior hypothalamus the release of endogenous histamine is modulated by H3 autoreceptors. Moreover, acetylcholine released from cholinergic neurons also modulates the release of histamine via M1 and/or M3 heteroreceptors.

Animals↗
PubMed1994

Release of acetylcholine in the ventral striatum is influenced by histamine receptors.

To investigate whether histamine receptor ligands influence the in vivo-release of acetylcholine in the ventral striatum, this brain region was superfused with histamine receptor agonists or antagonists through a push-pull cannula and drug effects on the release of acetylcholine were investigated. Histamine, the H1 receptor agonist 2-thiazolyl-ethylamine and the H3 receptor antagonist thioperamide enhanced acetylcholine release, while the H3 receptor agonist (R)-alpha-methylhistamine was ineffective. The results indicate that H1 receptors and H3 receptors modulate acetylcholine release. The thioperamide-induced increase of acetylcholine release might be exerted via H3-receptors located on cholinergic terminals. Alternatively, thioperamide might enhance acetylcholine release by increasing endogenous histamine release via H3 autoreceptors. It is concluded that, via stimulation of striatal H1- and H3 receptors, histaminergic neurons are involved in the regulation of cholinergic neuronal activity in the ventral striatum.

Acetylcholine↗
PubMed1993

Induction of GTP cyclohydrolase I by bacterial lipopolysaccharide in the rat.

A 2- to 3-fold increase of GTP cyclohydrolase I (E.C. 3.5.4.16), the key enzyme of tetrahydrobiopterin biosynthesis from GTP, was observed in cerebellum, remaining brain, liver, spleen, and adrenal gland of rats treated with a single dose of lipopolysaccharide (LPS). This led to increased biopterin levels in tissues but not in plasma. Parallel induction of nitric oxide (NO) synthase was indicated by a 10- to 100-fold increase of plasma nitrate levels 6 and 12 hours after injection of LPS. Furthermore, systolic blood pressure was reduced significantly by 23%. Our results demonstrate induction of tetrahydrobiopterin biosynthesis after LPS treatment in vivo.

Animals↗