Influence of lead exposure on catecholamine metabolism in discrete rat brain nuclei

1. Using the rat exposed both acutely and chronically to lead as a model of lead neurotoxicity, various parameters of catecholamine metabolism were investigated. 2. The steady-state concentrations of noradrenaline, adrenaline and dopamine together with the activities of tyrosine hydroxylase and phenylethanolamine N-methyl transferase were measured in discrete brain nuclei--periventricular, paraventricular, median eminence, posterior and anterior hypothalamus, caudate putamen and globus pallidus. 3. Lead exposure resulted in significant fall in the activity of the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase which was associated with alterations in concentrations of catecholamines in the median eminence, periventricular nucleus and anterior hypothalamus. 4. No other brain nuclei investigated exhibited any effect of lead on the catecholaminergic nervous system and, therefore, the effect of lead on rat brain can be considered to be regionally specific.     

Effect of a fall of blood pressure on the release of catecholamines in the hypothalamus

The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula and the release of endogenous catecholamines was determined in the superfusate which was continuously collected in 15 min periods. Fall in blood pressure elicited by nitroprusside or bleeding led to an increased rate of release of noradrenaline, adrenaline and dopamine in the hypothalamus. Transection of the brain causal to hypothalamus greatly reduced the rate of resting release of the catecholamines and abolished the enhancing effects of bleeding and nitroprusside. Determination of the catecholamines in samples which were collected in 90 s periods suggested a different pattern of release of the three catecholamines. Further shortening of the collection period (10 s) showed that the fall in blood pressure immediately increased the release of dopamine, while the rates of release of noradrenaline and adrenaline were increased gradually. Hypotension did not influence the rates of release of the catecholamines in the anterior hypothalamus. It is concluded that dopamine, adrenaline and noradrenaline systems of the hypothalamus are involved in the regulation of the arterial blood pressure. The different patterns of release might indicate that dopamine exerts a different function from those of noradrenaline and adrenaline in the normalization of the blood pressure after acute hypotension.     

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neuro-transmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.     

The mechanisms of the influence of the anterior and posterior hypothalamus on the electrical activity of the large hemispheres of the forebrain and on autonomic reactions in hens

Studies have been made of the effect of stimulation of the anterior and posterior hypothalamus on the electrical activity of the hemispheres, arterial blood pressure, heart and respiration rates. Mainly desynchronizing mechanisms were revealed in the ascending influences from both the anterior and posterior hypothalamus. Concerning the descending influences, it was found that stimulation of the anterior hypothalamus evokes depressor reactions, whereas stimulation of the posterior hypothalamus results in pressor reactions. Peculiarities of evolutionary development of the ascending and descending mechanisms of the posterior and anterior hypothalamus are discussed.     

Tyrosine content, influx and accumulation rate, and catecholamine biosynthesis measured in vivo, in the central nervous system and in peripheral organs of the young rat. Influence of neonatal hypo- and hyperthyroidism

The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.     

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ET(B) receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ET(C) receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.     

The brain catecholamines during domestication of the silver fox Vulpes fulvus

Studies have been made on the content of catecholamines (noradrenaline and dopamine) as well as metabolites of dopamine (3,4-dihydroxyphenylacetic and homovanillic acids) in the brain structures of silver foxes which differ in their handling reactions. The level of noradrenaline was found to be significantly higher in the anterior hypothalamus of domesticated animals; no differences in noradrenaline content were found in the frontal cortex, hippocamp, posterior hypothalamus and midbrain in animals from aggressive and domesticated groups. Dopamine content was higher in the tuberculum olfactorium of domesticated animals, being lower in the striatum and n. accumbens. Metabolite level remained unaffected which is presumably due to changes in dopamine synthesis in the investigated structures. It was concluded that domestication of animals favours the specimens with an altered state of catecholaminergic system of the brain.     

Changes in the innervational connections of the urinary bladder upon experimental stimulation of the hypothalamus]

The innervation of the urinary bladder was studied in 40 rabbits, 5 of which were control and in 35 animals the posterior and anterior nuclei of the hypothalamus were stimulated by electric current through bipolar electrodes. The efferent innervation connections in whose terminal plexuses there occurred absorption of catecholamines were shown histochemically and neurohistologically to be involved in the pathological process. Reactive and degenerative changes were found to take place in receptory nerve terminations, and first of all in free ones. Then the bodies of pseudounipolar neurons of spinal ganglia were changed. Changes were also found in the connections of sensory neurons with the cells of Goll's and Burdach's nuclei.     

Short-term regulation of tyrosine hydroxylase activity and expression by endothelin-1 and endothelin-3 in the rat posterior hypothalamus

Brain catecholamines are involved in several biological functions regulated by the hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate norepinephrine release in the anterior and posterior hypothalamus. As tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, the aim of the present work was to investigate the effects of ET-1 and ET-3 on TH activity, total enzyme level and the phosphorylated forms of TH in the rat posterior hypothalamus. Results showed that ET-1 and ET-3 diminished TH activity but the response was abolished by both selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788, respectively). In addition ET(A) and ET(B) selective agonists (sarafotoxin S6b and IRL-1620, respectively) failed to affect TH activity. In order to investigate the intracellular signaling coupled to endothelins (ETs) response, nitric oxide (NO), phosphoinositide, cAMP/PKA and CaMK-II pathways were studied. Results showed that N(omega)-nitro-l-arginine methyl ester and 7-nitroindazole (NO synthase and neuronal NO synthase inhibitors, respectively), 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one and KT-5823 (soluble guanylyl cyclase, and PKG inhibitors, respectively) inhibited ETs effect on TH activity. Further, sodium nitroprusside and 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and cGMP analog, respectively) mimicked ETs response. ETs-induced reduction of TH activity was not affected by a PKA inhibitor but it was abolished by PLC, PKC and CaMK-II inhibitors as well as by an IP(3) receptor antagonist. On the other hand, both ETs did not modify TH total level but reduced the phosphorylation of serine residues of the enzyme at positions 19, 31 and 40. Present results suggest that ET-1 and ET-3 diminished TH activity through an atypical ET or ET(C) receptor coupled to the NO/cGMP/PKG, phosphoinositide and CaMK-II pathways. Furthermore, TH diminished activity may result from the reduction of the phosphorylated sites of the enzyme without changes in its total level. Taken jointly present and previous results support that ET-1 and ET-3 may play a relevant role in the modulation of catecholaminergic neurotransmission in the posterior hypothalamus of the rat.     

Twenty-four hour rhythms of hypothalamic corticotropin-releasing hormone, thyrotropin-releasing hormone, growth hormone-releasing hormone and somatostatin in rats injected with Freund's adjuvant

The effect of Freund's adjuvant injection on 24-hour variation of hypothalamic corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), GH-releasing hormone (GRH) and somatostatin levels was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of rats receiving Freund's complete adjuvant or its vehicle 3 days before sacrifice were killed at six different time intervals throughout a 24-hour cycle. In the median eminence, adjuvant vehicle-injected rats exhibited significant 24-hour variations for the four hormones examined, with maxima at noon. These 24-hour rhythms were inhibited or suppressed by Freund's adjuvant injection. In the anterior hypothalamus of adjuvant vehicle-treated rats, CRH content peaked at 1600 h, while two peaks were found for TRH and GRH levels, i.e., at 2400-0400 h and 1600 h. Freund's adjuvant injection suppressed 24-hour rhythm of anterior hypothalamic CRH, TRH and GRH content and uncovered a peak in anterior hypothalamic somatostatin levels at 0400 h. In the medial hypothalamus of adjuvant vehicle-treated rats, significant 24-hour variations were detectable for TRH (peaks at 1600 and 2400 h) and somatostatin (peak at 2400 h) which disappeared after Freund's adjuvant injection. In the posterior hypothalamus of adjuvant vehicle-treated rats, two peaks were apparent for CRH, TRH and somatostatin levels, i.e. at 1600 h and 2400-0400 h, this hormonal profile remaining unmodified after Freund's adjuvant administration. The administration of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) impaired the depressing effect of Freund's adjuvant injection on CRH, TRH and somatostatin content in median eminence, but not that on GRH. In the anterior hypothalamus, cyclosporine generally prevented the effect of immunization on hormone levels an revealed a second maximum in TRH at 0400 h. Cyclosporine also restored 24-hour variations in TRH and somatostatin levels of medial hypothalamus of Freund's adjuvant-injected rats but was unable to modify them in the posterior hypothalamus. The results further support the existence of a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on hypothalamic levels which was partially sensitive to immunosuppression by cyclosporine.     

Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and posterior hypothalamus. Results showed that in the anterior hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V_max and the B_max whereas endothelin-1 decreased them. However, in the posterior hypothalamic region both endothelins diminished the V_max as well as B_max. Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K_d in the studied hypothalamic regions. These findings support that in the posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the hypothalamus.     

Growth hormone and prolactin secretion after hypothalamic deafferentation in pigs

Control of growth hormone (GH) and prolactin (PRL) secretion was investigated in ovariectomized, prepuberal Yorkshire gilts by comparing the effects of anterior (AHD), complete (CHD), and posterior (PHD) hypothalamic deafferentation with sham-operated controls (SOC). Blood samples were collected sequentially via an indwelling jugular catheter at 20-min intervals during surgery and recovery from anesthesia (Day 0) and Days 1 and 2 after cranial surgery. Mean serum concentrations of GH after AHD, CHD, and PHD were reduced (P less than 0.01) when compared with SOC gilts. Furthermore, episodic GH release evident in SOC animals was obliterated after hypothalamic deafferentation. PRL concentrations in peripheral serum of hypothalamic deafferentated gilts remained similar (P greater than 0.05) to those of SOC animals. These results indicate that anterior and posterior hypothalamic neural pathways play a minor role in the control of PRL secretion in the pig in as much as PRL levels remained unchanged after hypothalamic deafferentation. These findings may be interpreted to suggest that the hypothalamus by itself seems able to maintain tonic inhibition of PRL release. In contrast, the maintenance of episodic GH secretion depends upon its neural connections traversing the anterior and posterior aspects of the hypothalamus in the pig.     

Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and posterior hypothalamus. Results showed that in the anterior hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V_max and the B_max whereas endothelin-1 decreased them. However, in the posterior hypothalamic region both endothelins diminished the V_max as well as B_max. Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K_d in the studied hypothalamic regions. These findings support that in the posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the hypothalamus.     

An analysis of the hypothalamic mechanisms regulating cold hypobiosis in the frog Rana temporaria]

Experiments were made on intact frogs and after removal the anterior or the posterior hypothalamus. Data of spectral analysis of the EEG as well as quantitative evaluation of activation phenomena occurring spontaneously during hypobiosis are presented. Removal of the anterior hypothalamus did not affect the EEG parameters investigated, whereas lesion of the posterior hypothalamus significantly decreased cold-resistance capacities in frogs.     

The effects of reserpine and haloperidol on tyrosine hydroxylase activity in the brains of aged rats

Many neurotransmitter systems appear to be altered with aging. The effects of aging on the regulation of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines in the brain has been examined. The endogenous basal activity of tyrosine hydroxylase was lower in the hypothalamus of 24 month old Fisher 344 rats than in the hypothalamus of 3 month old or 6 month old animals. There was no difference in the basal activity of tyrosine hydroxylase in the locus ceruleus, frontal cortex, hippocampus, substantia nigra, or the striatum of rats of ages 3 months, 6 months and 24 months. Tyrosine hydroxylase activity was increased in the striatum of 3 month old (60%) and 6 month old (28%) rats after treatment with haloperidol or reserpine, whereas no change in enzyme activity followed administration of these drugs to 24 month old animals. In conclusion, increases in tyrosine hydroxylase activity in the brain that normally occur in the striatum of 3 month old rats after haloperidol or reserpine treatment are significantly decreased in 6 month old rats and not apparent in 24 month old rats.     

The distribution of monoamines in the hypothalamus of the Japanese quail Coturnix coturnix japonica

Summary The distribution of monoamines in the hypothalamus of the Japanese quail (Coturnix coturnix japonica) has been studied using a histochemical fluorescence technique. In the posterior hypothalamus catecholamine-containing nerve fibres are localised in the nucleus tuberis and nucleus hypothalamicus posterior medialis and are linked by fluorescent tracts running in the stratum cellulare internum. Further tracts may be traced from the nucleus tuberis around the base of the third ventricle to the sub-ependymal layer of the median eminence, where they then appear to pass through the hypothalamo-hypophysial neurosecretory tract to terminate in the palisade zone on the portal vascular bed. The innervation of the palisade layer by catecholamines is sparse. The fluorescent terminals are spread evenly throughout both the anterior and posterior divisions of the median eminence. There is no monoamine innervation of the pars nervosa. The paraventricular organ has both 5-hydroxytryptamine- and catecholamine-containing cell bodies and axons may be traced into the region of the nucleus hypothalamicus posterior medialis. In the anterior hypothalamus the neurosecretory paraventricular nucleus contains many catecholamine nerve fibres and terminals. These are linked by fibre tracts to the nucleus basalis and to the nucleus hypothalamicus posterior medialis. The supraoptic nucleus is less well innervated although a dense accumulation of fibres lies in the preoptic recess. The latter is thought to give rise to long axons which pass in association with the neurosecretory tract to end in the nucleus tuberis.Supported by a Grant (AG 24/36) from The Agricultural Research Council. We are indebted to Dr. G. A. Clayton, Institute of Animal Genetics, University of Edinburgh, for supplying the birds.     

自发性高血压大鼠中枢血管紧张素Ⅱ的变化对中枢肾上腺素...

The content of norepinephrine (NE) and epinephrine (E) in the brain of spontaneously hypertensive rats has proved abnormal, but the cause remained unknown. It was shown in the recent work that NE content in pons, posterior hypothalamus, nucleus caudatus and E concentration in medulla oblongata, anterior and posterior hypothalamus of 12-week old stroke-prone spontaneously hypertensive rats (SHRSP) were much higher than those of age-matched Wister-Kyoto rats (WKY). SHRSP also showed higher levels of systolic blood pressure (SBP) and brain angiotensin II (A II) than WKY. Intracerebroventricular (icv) perfusion of angiotensin-converting enzyme inhibitor captopril (20 micrograms for each time and three times for each day for four weeks) inhibited the synthesis of brain A II and reduced SBP and NE, E contents in all examined brain areas in SHRSP and WKY. However, the effects of chronically perfused captopril on SBP and brain NE, E levels in SHRSP were much more significant than in WKY. The results indicate that the modulatory effects of central renin-angiotensin system (RAS) on central adrenergic and noradrenergic system might be overactivated in SHRSP, which might partially responsible for the abnormally high levels of NE, E in some of the brain areas of SHRSP.     

Effect of dietary proteins and carbohydrates on urinary and sympathoadrenal catecholamines

We previously observed that administration of tyrosine to rats or humans elevated urinary dopamine, norepinephrine and epinephrine levels. The present studies examine the effects on these urinary catecholamines of varying the ratio of protein to carbohydrate in the diets.Rats consumed diets containing 0, 18 or 40% protein (76, 58 and 36% carbohydrate respectively) for 8 days. The stress of consuming the protein-free food was associated with a 16% weight reduction, and with significantly lower serum, heart and brain tyrosine levels than those noted in rats eating the 18 or 40% protein diets. Absence of protein from the diet also decreased urinary levels of dopamine and DOPA but increased urinary norepinephrine and epinephrine, probably by increasing sympathoadrenal discharge; it also increased the excretion of DOPA in animals pretreated with carbidopa, a DOPA decarboxylase inhibitor. Carbidopa administration decreased urinary dopamine, norepinephrine and epinephrine as expected; however, among carbidopa-treated rats urinary norepinephrine and epinephrine concentrations were highest for animals consuming the protein-free diet, again suggesting enhanced release of stored catecholamines from sympathoadrenal cells. The changes in urinary catecholamines observed in animals eating the protein-free diet were similar to those seen in rats fasted for 5 days: dopamine levels fell sharply while norepinephrine and epinephrine increased.These data indicate that the effects of varying dietary protein and carbohydrate contents on dopamine secretion from peripheral structures differ from its effects on structures secreting the other two catecholamines. Protein consumption increases dopamine synthesis and release probably by making more of its precursor, tyrosine, available to peripheral dopamine-producing cells; it decreases urinary norepinephrine and epinephrine compared with that seen in protein-deprived animals, probably by diminishing the firing of sympathetic neurons and adrenal chromaffin cells.     

Effects of lipopolysaccharide on neurokinin A content and release in the hypothalamic-pituitary axis

The administration of bacterial lipopolysaccharide (LPS) markedly affects pituitary secretion, and its effects are probably mediated by cytokines produced by immune cells or by the hypothalamo-pituitary axis itself. Since neurokinin A (NKA) plays a role in inflammatory responses and is involved in the control of prolactin secretion, we examined the in vivo effect of LPS on the concentration of NKA in hypothalamus and pituitary (assessed by RIA) and serum prolactin levels in male rats. One hour after the intraperitoneal administration of LPS (250 microg/rat), NKA content was decreased in the posterior pituitary but not in the hypothalamus or anterior pituitary. Three hours after injection, LPS decreased NKA concentration in the hypothalamus and anterior and posterior pituitary. In all the conditions tested, LPS significantly decreased serum prolactin. We also examined the in vitro effects of LPS (10 microg/ml), interleukin-6 (IL-6, 10 ng/ml) and tumor necrosis factor alpha (TNF-alpha, 50 ng/ml) on hypothalamic NKA release. Interleukin-6 increased NKA release without modifying hypothalamic NKA concentration, whereas neither LPS nor TNF-alpha affected them. Our results suggest that IL-6 may be involved in the increase of hypothalamic NKA release induced by LPS. NKA could participate in neuroendocrine responses to endotoxin challenge.     

Histamine-immunoreactive neurons in the hypothalamus of cats

The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine-immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus.