Modulation of histamine release in the hypothalamus by nitric oxide.
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Animals↗
Biomedical subjects
A Philippu
Publications and source records attributed to A Philippu.
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↗
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↗
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.
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Corticotropin-releasing factor modulates basal and stress-induced excitatory amino acid release in the locus coeruleus of conscious rats.
The in vivo interactions between corticotropin-releasing factor (CRF) and excitatory amino acid (EAA) release in the locus coeruleus (LC) were studied. Superfusion of the LC with CRF (0.1 microM) led to a prolonged increase in the release rate of aspartate and, to a lesser extent, of glutamate. The CRF antagonist alpha-helical CRF9-41 (1 microM) had no effect on basal EAA release but abolished the enhanced aspartate and glutamate release induced by noise stress (95 dB). Tail pinch-induced EAA release was not influenced by alpha-helical CRF9-41. Results demonstrate a facilitatory action of CRF on in vivo EAA release in the LC. Furthermore, modulation by CRF of stress-induced EAA release in the LC depends on the nature of stress.
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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↗
Involvement of biogenic amines and amino acids in the central regulation of cardiovascular homeostasis.
Biogenic amines and amino acids have been implicated in central cardiovascular homeostasis. Initially, drugs were injected into the brain and their effects on blood pressure were investigated. Other approaches allowed endogenous neurotransmitters released in the extracellular space of brain structures involved in cardiovascular regulation to be identified. As Nicolas Singewald and Athineos Philippu outline, even slight disturbances in blood pressure and/or isovolaemia lead to marked changes in the release rates of biogenic amines and amino acids in various brain structures. Blood pressure homeostasis is maintained with the participation of several brain regions and neurotransmitters which possess the same or opposing functions when released from CNS neurones.
Amino Acids↗
Serotonin outflow in the hypothalamus of conscious rats: origin and possible involvement in cardiovascular control.
The push-pull technique was used to investigate the effects of neuroactive compounds and experimentally induced blood pressure changes on the release of endogenous serotonin in the posterior hypothalamic area of the rat. Hypothalamic superfusion with artificial cerebrospinal fluid which contained 80 mM K+ or 1 microM veratridine enhanced the rate of serotonin release. Superfusion with tetrodotoxin (5 microM) led to a pronounced decrease in the serotonin release rate. Increases in blood pressure elicited by intravenous infusions of noradrenaline (3-4 micro g/kg/min) or phenylephrine (10 microg/kg/min) enhanced the release of serotonin in the hypothalamus. Similarly, the serotonin release rate was enhanced by hypervolaemia. Decreases in blood pressure elicited by intravenous administration of nitroprusside (30-40 microg/kg/min) or chlorisondamine (3 mg/kg) reduced the release of serotonin. Likewise, the serotonin release rate was decreased by hypovolaemia. With one exception (hypothalamic superfusion with tetrodotoxin) neither neuroactive drugs, nor experimentally elicited blood pressure changes modified the release rate of the metabolite 5-hydroxyindoleacetic acid (5-HIAA). These findings show that changes in blood pressure lead to counteractive alterations in the release of serotonin. Thus, serotoninergic neurons of the posterior hypothalamus seem to be involved in the homeostasis of blood pressure by exerting a hypotensive function. At least in the hypothalamus, the concentration of 5-HIAA in the superfusate does not seem to be a reliable marker for the activity of serotoninergic neurons.
Animals↗
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↗
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↗
Inhibition of catecholamine (noradrenaline, dopamine) release in the locus coeruleus and the hypothalamus by baroreceptor activation: identification of the involved baroreceptors.
We have previously shown that experimentally induced blood pressure changes modify the release rates of catecholamines in the hypothalamus and the locus coeruleus. The aim of the present investigation was to identify the peripheral baroreceptors and the centripetal pathways responsible for the changes of catecholamine release in these brain areas. In anaesthetized cats, push-pull cannulae were bilaterally inserted into the locus coeruleus and the posterior hypothalamus. The two brain areas were superfused simultaneously with artificial cerebrospinal fluid. Baroreceptor activation by phenylephrine-induced blood pressure elevation decreased the release rate of noradrenaline in the locus coeruleus and the release rates of noradrenaline and dopamine in the posterior hypothalamus. Similar effects were elicited by electrical stimulation of the central trunk of the transected vagus and aortic depressor nerves (vagus-ADN). Transection of the nerves abolished the effect of phenylephrine on the release of noradrenaline in the locus coeruleus. Nerve transections attenuated slightly the decreased release of noradrenaline elicited by phenylephrine in the posterior hypothalamus, while the reduced dopamine release rate was not influenced. The selective stimulation of baroreceptors in the carotid sinus by an inflatable catheter did not influence the release of catecholamines in the locus coeruleus, while release rates of noradrenaline and dopamine in the posterior hypothalamus were decreased. The simultaneous superfusion of locus coeruleus and hypothalamus revealed that, in both areas, noradrenaline release is inhibited by baroreceptor activation. Noradrenergic neurons of the posterior hypothalamus are inhibited by baroreceptor impulses conducted by the carotid sinus nerve and vagus-ADN, while the noradrenergic neurons of the locus coeruleus seem to respond to impulses transmitted by vagus-ADN.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
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↗
Ionic and haemodynamic changes influence the release of the excitatory amino acid glutamate in the posterior hypothalamus.
The push-pull technique was used to investigate the release of the excitatory amino acid glutamate in the posterior hypothalamic area of the conscious rat. The hypothalamus was superfused through the push-pull cannula with artificial cerebrospinal fluid (CSF), and the superfusate was collected in time periods of 10 min when ionic conditions in the CSF were changed, or in short periods of 3 min when blood pressure changes were evoked. The mean glutamate release rate was 2.8 +/- 0.7 pmol/min. Depolarization by hypothalamic superfusion with CSF containing 50 mM K+ enhanced the release of glutamate in the presence of Ca2+. The K(+)-induced release was attenuated by 40% when the hypothalamus was superfused with Ca(2+)-free CSF. Replacement of Ca2+ by Mg2+ abolished the K(+)-induced release of glutamate. Hypovolaemia elicited by haemorrhage enhanced the release rate of glutamate. Similarly, a hypotension elicited by i.v. injection of chlorisondamine (3 mg/kg) led to a pronounced and permanent enhancement in glutamate release. The effects of hypovolaemia and chlorisondamine on glutamate release were abolished in aortic denervated rats, indicating that this response is due to a decrease of impulse generation in baroreceptors. A hypervolaemia elicited by blood infusion did not affect the release of glutamate. Similarly, a pronounced pressor response to phenylephrine (15 micrograms/kg per minute) infused intravenously for 9 min was ineffective. The results show that the K(+)-induced release of glutamate in the hypothalamus is dependent on the presence of Ca2+. The increase in glutamate release rate by hypovolaemia or chlorisondamine suggests that the glutamatergic neurons in the posterior hypothalamic area respond to unloading of aortic baroreceptors and possess a counteracting, hypertensive function.
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Effects of neuroactive compounds, noxious and cardiovascular stimuli on the release of amino acids in the rat locus coeruleus.
The release of excitatory amino acids (glutamate, aspartate), inhibitory amino acids (GABA, taurine) and arginine was determined in the locus coeruleus (LC) of anaesthetized rats. The neuronal origin of stimulated amino acid release was verified by superfusion with neuroactive compounds. Electrical stimulation of the sciatic nerve, as well as mechanical footshock, enhanced LC release rates of glutamate and aspartate without influencing those of taurine and arginine. GABA release rate was increased slightly after some delay. Excitatory amino acid release was not influenced by changes in blood pressure. The results provide direct neurochemical evidence that noxious stimuli activate LC neurons via the glutamate and aspartate input into this nucleus.
Amino Acids↗
Disturbances in blood pressure homeostasis modify GABA release in the locus coeruleus.
The locus coeruleus (LC) of anaesthetized rats was superfused with artificial cerebrospinal fluid through a push-pull cannula and the release of the amino acids gamma-aminobutyric acid (GABA), taurine and arginine was determined in the superfusate. Increases in blood pressure (BP) induced either by intravenous infusions of noradrenaline and phenylephrine or by blood injection enhanced the release of GABA in the LC. Decreases in BP elicited by intravenous infusion of sodium nitroprusside or by haemorrhage decreased the GABA release rate. The BP changes did not influence the release rates of taurine and arginine. These findings demonstrate that GABA release in the LC is modified by cardiovascular impulses and suggest that GABAergic neurones modulate LC activity in response to disturbances in BP homeostasis.
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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↗
In vivo release of catecholamines in the locus coeruleus.
To investigate the release of endogenous dopamine, noradrenaline and adrenaline in the locus coeruleus, this brain area was superfused with artificial cerebrospinal fluid (CSF) through push-pull cannulae and the release of catecholamines was determined in the superfusate radioenzymatically. Collection of superfusates in time periods of 10 min revealed that release rates of the three catecholamines fluctuated, thus pointing to the existence of ultradian rhythms with following mean periods (minutes per cycle): noradrenaline 52 +/- 4, dopamine 37 +/- 2, adrenaline 36 +/- 2. The rhythm frequency of noradrenaline was significantly lower than the frequencies of dopamine and adrenaline. When the locus coeruleus was superfused with neuroactive drugs, superfusates were collected in time periods of 3 min. Superfusion with tetrodotoxin (1 mumol l-1) for 12 min elicited a prompt and sustained decrease (-70%) in the release rates of dopamine and adrenaline. The release rate of noradrenaline was also reduced, although to a lesser extent (-40%). Superfusion with veratridine (50 mumol l-1) led to an immediate and very pronounced enhancement in the release rates of dopamine, noradrenaline and adrenaline. The veratridine-induced increase in catecholamine outflow was decreased strongly by simultaneous superfusion with tetrodotoxin. The findings suggest that the release of endogenous catecholamines in the locus coeruleus fluctuates according to ultradian rhythms. Changes in the release on superfusion with veratridine and tetrodotoxin demonstrate the neuronal origin of the three catecholamines. The observed differences in the release characteristics between noradrenaline on the one hand and dopamine and adrenaline on the other might indicate that noradrenaline is partly released from somatodendritic sites of the noradrenergic cell bodies in the locus coeruleus.
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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↗