Neuropeptide Y in hamster limbic nuclei: lack of colocalization with substance P

The medial nucleus of the amygdala (Me), bed nucleus of the stria terminalis (BNST), and medial preoptic area (MPOA) regulate copulation in the male hamster. The present study identified neuropeptide Y-immunoreactive (NPY-IR) neurons in the BNST and Me with the greatest concentration in the posteromedial and posteriordorsal subdivisions of these nuclei, respectively. NPY-IR filters are found in all three nuclei with dense plexi of NPY-IR varicosities in the most medial subdivisions. Substance P neurons are also densely concentrated in the posterior BNST and Me; however, no neurons contained both peptides. Thus, NPY and substance P neurons comprise two distinct populations within the BNST and Me of the hamster.     

Neuropeptide Y and cardiovascular regulation

Neuropeptide Y is a vasoactive peptide and is widely distributed throughout the central and peripheral nervous systems. Neuropeptide Y is co-released with noradrenaline by perivascular nerve endings. At high concentrations, it has a direct vasoconstrictor effect. In addition, it enhances the vascular effect of various agonists, including noradrenaline and angiotensin II. Moreover, neuropeptide Y has an inhibitory effect on renin secretion. This peptide may have an important role in cardiovascular regulation.     

Neuropeptide Y and luteinizing hormone releasing hormone synergize to stimulate the development of cellular follicle-stimulating hormone in the hamster adenohypophysis

Luteinizing hormone releasing hormone (LHRH) stimulates the development of cellular FSH immunoreactivity in the perinatal hamster adenohypophysis. Because neuropeptide Y (NPY) can act directly on rat adenohypophysial cells to stimulate FSH and LH release and potentiate the stimulatory effect of LHRH on FSH and LH release, we investigated the effects of NPY alone and in combination with a low, ineffective dose of LHRH on inducing cellular FSH immunoreactivity in the neonatal hamster adenohypophysis. Neonatal female pituitary glands were grafted beneath the right renal capsules of hypophysectomized-ovariectomized adult hamster hosts with a catheter implanted in the external jugular vein. After treatment, hosts were decapitated and graft tissue was stained for FSH and LH immunoreactivity. The mean percentage of adenohypophysial cells that stained for FSH was low (2.8%) in grafts in hosts infused continuously with heparinized saline vehicle for 7 days. In other hosts, peptides were pulsed through the catheter every 12 h for 7 days. The mean percentage of FSH cells also was low after pulsing 6 ng LHRH or 2 micrograms NPY but increased substantially when the two peptides were pulsed simultaneously. No differences in the mean percentage of LH cells existed between any of the groups. The results demonstrate that NPY and LHRH can synergize to induce cellular FSH immunoreactivity in the neonatal female hamster.     

Neuropeptide Y in the human prenatal and mature gonads

The in vitro effects of a trace element preparation (béres Drops Plus, BDP) on the biosynthesis of inflammatory cytokines interleukin (IL-6, IL-1, and tumor necrosis factor-alpha (TNF-alpha) were studied in human peripheral monocytes. The production of IL-6 was studied in a glioblastoma cell line, SKMG-4, as well. The trace element preparation BDP significantly stimulated both the constitutive and the endotoxin or IL-1 induced IL-6 production in monocytes or in glial cells, respectively, but revealed no or only modest effect on IL-1 and TNF-alpha production of monocytes. Moreover, BDP was able to reduce the inhibitory effect of a synthetic corticosteroid, dexamethasone on the biosynthesis of IL-6. The positive effect of the trace element preparation on the IL-6 production of monocytes from rheumatoid arthritis (RA) patients is comparable, to that of on the monocytes from healthy individuals, and similarly to healthy individuals was negligible on the IL-1 and TNF-alpha production. The detailed analysis of the composition of the preparation suggested, that the major active component in the stimulation of IL-6 production is Zn, but for the complete effect other trace elements are also required.     

Neuropeptide immunoreactivity in ligature-induced neuromas of the inferior alveolar nerve in the ferret

Injury to branches of the trigeminal nerve can sometimes result in persistent dysaesthesia. In an attempt to understand the aetiology of this condition we are currently investigating changes which occur at the injury site. In the present study we have examined the expression of seven neuropeptides, all of which have been implicated in nociceptive transmission, or have previously been shown to have altered expression following nerve injury. In 20 adult ferrets the inferior alveolar nerve was sectioned and ligated, and recovery permitted for 3 days, 8 days, 3 weeks, 6 weeks or 12 weeks. Longitudinal sections of the neuromas were processed using immunohistochemical techniques to quantify the expression of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, somatostatin, enkephalin and neuropeptide Y. After 3 days, all of the neuropeptides were expressed at the injury site. In the neuromas examined after longer recovery periods these levels of expression had declined and were similar to those found in the contralateral controls. This initial high level, followed by a decline, parallels the incidence of ectopic neural activity recorded electrophysiologically in the same model. It is, therefore, possible that the accumulation of neuropeptides at the injury site may play a role in the initiation or modulation of ectopic neural activity.     

Neuropeptide Y1 receptors in the rat genital tract

Using in situ hybridization and immunohistochemistry, the expression of type 1 neuropeptide Y (NPY) receptors (Y1-Rs) has been demonstrated in the rat genital tract. In the male Y1-R mRNA and Y1-R-like immunoreactivity (LI) were found in smooth muscles of predominantly arterioles and small arteries inside testis. Fibers showing NPY-LI could not be detected within testis but only in the tunica albuginea. These Y1-Rs are suggested to mediate vasoconstriction, possibly activated by NPY released from nerves in the tunica albuginea. In the female rat Y1-R mRNA, but not Y1-R-LI was found in vascular smooth muscles of arteries in the ovary and oviduct. In the oviduct Y1-R mRNA was also detected in the non-vascular smooth muscle layer. Fibers showing NPY-LI were found around blood vessels both in the ovary and oviduct. In the female genital tract also Y1-Rs may thus be involved in regulatory mechanisms mediating, for example, vasoconstriction.     

Neuropeptide Y in cortisol-induced hypertension in male volunteers

1. Cortisol-induced blood pressure rises in men are not accompanied by increases in plasma catecholamines. The present study examines the effects of cortisol on the sympathetic co-transmitter, neuropeptide Y (NPY). 2. Eight normal men were given cortisol 200 mg/day over 5 days and haemodynamic, metabolic and hormonal measures were taken. Plasma NPY-like immunoreactivity (NPY-LI) concentrations were measured by direct radio-immunoassay. 3. Cortisol significantly increased systolic, diastolic and mean arterial pressure, bodyweight, plasma glucose and total white cell concentration and decreased plasma potassium and total eosinophil count, as in previous studies. Plasma NPY concentrations were not altered significantly during cortisol treatment, but increased following cessation of cortisol treatment (P = 0.006). 4. The essentially unchanged pattern for NPY concentration with cortisol treatment resembles that previously reported for adrenaline and noradrenaline, but the increase in NPY on cortisol withdrawal was not seen for adrenaline or noradrenaline. These data do not support a role for sympathetic activation in the genesis of cortisol-induced hypertension.     

Neuropeptide Y phase shifts the circadian clock in vitro via a Y2 receptor

The suprachiasmatic nuclei (SCN) contain a circadian clock whose activity can be recorded in vitro for several days. This clock can be reset by the application of neuropeptide Y. In this study, we focused on determination of the receptor responsible for neuropeptide Y phase shifts of the hamster circadian clock in vitro. Coronal hypothalamic slices containing the SCN were prepared from Syrian hamsters housed under a 14 h:10 h light:dark cycle. Tissue was bathed in artificial cerebrospinal fluid (ACSF), and the firing rates of individual cells were sampled throughout a 12 h period. Control slices received either no application or application of 200 nl ACSF to the SCN at zeitgeber time 6 (ZT6; ZT12 was defined as the time of lights off). Application of 200 ng/200 nl of neuropeptide Y at ZT6 resulted in a phase advance of 3.4 h. Application of the Y2 receptor agonist, neuropeptide Y (3-36), induced a similar phase advance in the rhythm, while the Y1 receptor agonist, [Leu31, Pro34]-neuropeptide Y had no effect. Pancreatic polypeptide (rat or avian) also had no measurable phase-shifting effect. Neuropeptide Y applied at ZT20 or 22 had no detectable phase-shifting effect. These results suggest that the phase-shifting effects of neuropeptide Y are mediated through a Y2 receptor, similar to results found in vivo.     

Neuropeptide Y stimulates bile secretion via Y1 receptor in the left dorsal vagal complex in rats

Neuropeptide Y (NPY) injected into the cerebrospinal fluid and the left dorsal vagal complex enhances bile acid-independent and bicarbonate-dependent bile secretion through vagal muscarinic pathways in animal models. NPY binds to and activates six different receptor subtypes, and NPY Y1 and Y2 receptors are distributed in the dorsal vagal complex. We sought to determine which NPY receptor subtypes are involved in central stimulation of bile secretion by examining the effect of microinjection of specific NPY receptor agonists into the dorsal vagal complex. The bile duct was cannulated in urethane-anesthetized and bile acid-compensated rats. After measuring basal secretion, NPY, peptide YY (PYY), [Leu31, Pro34]NPY, NPY(13-36), or NPY(3-36) was microinjected into the either right or left dorsal vagal complex and bile secretion was observed for 100 minutes. Hepatic branch vagotomy was performed 2 hours before the peptide injection. Microinjection of NPY and PYY (8 pmol) into the left dorsal vagal complex increased bile secretion. [Leu31, Pro34]NPY microinjected into the left dorsal vagal complex also dose-dependently (1-8 pmol) stimulated bile acid-independent and bicarbonate-dependent bile secretion. Microinjection of NPY(13-36) into the left dorsal vagal complex did not stimulate and NPY(3-36) dose-dependently inhibited bile secretion. Stimulation of bile secretion by [Leu31, Pro34]NPY was abolished by hepatic branch vagotomy. NPY acts in the left dorsal vagal complex to stimulate bile acid-independent and bicarbonate-dependent bile secretion via Y1 receptor subtype.     

Neuropeptide Y potentiates norepinephrine-stimulated inositol phosphate production in the rat tail artery

In our cross-sectional study we investigated the separate influence of three main factors, namely menopausal and estrogen status, and chronological age, on ten neurovegetative climacteric complaints reported in the scale of Kupperman et al. A multivariate statistical analysis was performed by a multivariate statistical approach on 1161 untreated women seen at the Menopause Center of the Ferrara University Hospital. Ninety women (age range, 41-54 years) were premenopausal; 492 women (age range, 38-55 years) were perimenopausal with irregular periods or amenorrhea for less than 12 months; 468 women (age range, 41-69 years) had a spontaneous menopause (age range, 37-66 years); 111 had had hysterectomy with bilateral ovariectomy while still regularly menstruating. Serum estrone was used as the indicator of the patients' estrogen status. A clear positive trend was demonstrated between menopausal status and the prevalence of depression, hot flushes, insomnia and joint pain. However, only the prevalence of hot flushes amongst these four symptoms was significantly related with the climacteric estrogen decline (beta = -0.006, P = 0.001). Moreover, menopausal status appeared to influence the intensity of fatigue, hot flushes, insomnia and paresthesia. Age was found to significantly (P = 0.053) co-vary only with the intensity of the hot flushes, with a positive relation (beta = 0.092, r = 0.104, P = 0.003), whereas estrone values did not significantly co-vary with any symptom. Furthermore, while neurovegetative symptoms are largely present also in the absence of hot flushes, when these latter are present, they exacerbate both the intensity and the prevalence of all the other symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropeptide Y antibody attenuates 2-deoxy-D-glucose induced feeding in rats

2-deoxy-D-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake.     

Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells

OBJECTIVE: The food selection and nutrient intake were investigated in women with anorexia nervosa, bulimia nervosa and controls. METHODS: Dietary data was obtained by 24-hour recall, and 7-day recording among eating disordered patients, and by 3-day registration among controls. RESULTS: The intake of energy and nutrients differed from controls, as expected, while there were no differences between anorectics and bulimics in this respect, except for iron. There were only minor differences among the three groups studied with respect to nutrient density. Energy percentages of protein, fat, and carbohydrates, were similar in all groups, but a subdivision of the macronutrients into respective sources showed that bulimics had a lower relative and absolute intake of carbohydrates from bread and cereals than anorectics and controls. CONCLUSION: Eating disorder patients, despite their marginal food intake, still met the minimum requirement for most nutrients according to the Nordic Nutrient recommendations.     

Neuropeptide Y in relation to carbohydrate intake, corticosterone and dietary obesity

Bone morphogenetic proteins (BMPs) perform diverse functions in vertebrate development. Here we demonstrate that the heterodimeric BMP-4/7 protein directly induces ventral mesoderm and blood in Xenopus animal caps, and BMP-2/7 heterodimers may function similarly. We also provide indirect evidence that BMP heterodimers function in embryos, using assays with dominant-negative BMP ligands. Homodimeric BMP-2 and BMP-4 proteins do not induce mesoderm, but they ventralize mesoderm induction by activin. In contrast, BMP-7 protein interferes with mesoderm induction by activin, but BMP-7 stimulates ventral mesoderm induction by the heterodimer, BMP-4/7. This novel property of BMP-7 distinguishes it from other BMPs. BMP-7 may therefore function in early embryogenesis to antagonize activin signals and potentiate BMP signals. We propose that BMP heterodimers convey signals for ventral mesoderm induction and patterning in Xenopus development.     

Somatovisceral projections from spinal cord and dorsal column nuclei to the thalamus in hedgehog tenrecs

In order first to overcome the difficulties in understanding the increasing amount of information available regarding the mammalian somatosensory thalamus, and then to correlate the findings among different species and integrate them into a general concept of thalamic organization, the present study investigated the spinothalamic and medial lemniscal projections in Madagascan hedgehog tenrecs (Echinops telfairi and Setifer setosus). Tracer substances were injected into the dorsal column nuclei and into spinal segments at various levels; additional injections were made into the inferior colliculus. The ascending somesthetic projections were to predominantly contralateral posterolateral target areas, and were almost mirror-like on both sides to intralaminar and medial thalamic nuclei. The densest and most extensive projections, originating mainly from the high cervical spinal cord and the dorsal column nuclei, reached the posterolateral thalamus caudal to the lateral geniculate nucleus. This region was difficult to subdivide cytoarchitecturally; nevertheless, on the basis of its labeling pattern, several subdivisions could be described and preliminary named. Some of them compared tentatively with the internal portion of the medial geniculate nucleus (GM) and the ventral posterior nuclear complex (VPC) in more differentiated mammals. The most prominent subdivision, however, located subjacent to the lateral surface of the brainstem, was shown to receive additional fibers from the inferior colliculus. This region might be considered a further subdivision of GM, VPC, a perigeniculate area, and/or a region of its own not comparable at present, with thalamic regions in other mammals. On the other hand, it may also be a remnant of the hypothetical, diffuse multimodal region from which GM and VPC have possibly evolved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calretinin immunoreactivity in the developing thalamus of the rat: a marker of early generated thalamic cells

The present work was aimed to study the immunocytochemical localization of the calcium-binding protein, calretinin, in the rat thalamus from embryonic day 14 to the third postnatal week. In the adult rat thalamus, calretinin immunoreactivity is intensely expressed in some intralaminar and midline nuclei, as well as in selected regions of the reticular nucleus. At embryonic day 14, calretinin was expressed by immature and migrating neurons and fibres laterally to the neuroepithelium of the diencephalic vesicle in the region identified as reticular neuroepithelium. At embryonic day 16, immunoreactive neurons were present in the primordium of the reticular nucleus and in the region of the reticular thalamic migration, where neurons showed the morphology of migratory cells. At the end of embryonic development and in the first postnatal week, calretinin-positive neurons were observed in selected region of the reticular nucleus and it was intensely expressed in some intralaminar and midline nuclei. Bands of immunopositive fibres were also observed crossing the thalamus. During the second postnatal week, the immunolabelling in the reuniens, rhomboid, paraventricular and central medial thalamic nuclei remains very intense while a decrease of immunoreactivity in mediodorsal, centrolateral and laterodorsal nuclei was observed. The immunostaining of fibres, particularly evident in the perinatal period, progressively decreased and it was no longer visible by the end of the second postnatal week when the distribution and intensity of calretinin immunostaining was similar to that observed in the adult rat thalamus. The present findings indicate that the immunolocalization of calretinin can be used to identify subsets of thalamic neuronal population during pre- and postnatal maturation allowing also the detection of the migratory pattern of early generated reticular thalamic neurons.     

Neuropeptide Y: a novel link between the neuroendocrine system and cholesterol metabolism

High serum total and low-density lipoprotein (LDL) cholesterol levels constitute the main risk factor for atherosclerotic vascular diseases. Both genetic and environmental factors are involved in the regulation of serum cholesterol levels. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, is known to regulate food intake and energy balance but its role in cholesterol metabolism has remained almost untouched in former literature. A newly discovered association between a leucine(7)-to-proline(7) polymorphism (Pro(7)) in the signal peptide of NPY and a high cholesterol level may provide new ideas for the genetic regulation of cholesterol metabolism. The presence of the Pro(7) in NPY results in serum total cholesterol levels 0.6-1.4 mmol/L higher compared with subjects without this gene variant. The Pro(7) in NPY was detected in 14% of Finns but only in 6% of Dutchmen, and its impact on serum cholesterol concentration seems to be stronger in obese than in normal-weight subjects. At least among Finns, the Pro(7) in NPY is one of the strongest genetic factors identified thus far affecting serum cholesterol levels.     

Monoclonal antibody Cat-301 selectively identifies a subset of nuclei in the cat's somatosensory thalamus

Recently it has been demonstrated that the monoclonal antibody Cat-301 is capable of identifying functionally related neurons in the mammalian visual thalamus. We have examined the possibility that this antibody might display a similar capacity in nonvisual thalamic areas. We demonstrate that in the cat's somatosensory thalamus the distribution of Cat-301-positive cells and neuropil is restricted to a subset of nuclei. These include the ventroposterior medial, ventroposterior lateral, and ventroposterior inferior nuclei. Staining with Cat-301 provides a clear visualisation of the entire somatotopic map within these nuclei. The somatosensory sector of the thalamic reticular nucleus and the perireticular nucleus, which may have a somatosensory sector, are also Cat-301-positive. In contrast, cells that do not express the Cat-301 antigen are located in the ventroposterior oralis nucleus, the ventroposterior shell region, the medial and lateral divisions of the posterior nuclear group, and the inner small cell region adjacent to the thalamic reticular nucleus. In comparison with previous physiological studies, cells that express the Cat-301 antigen most likely represent subpopulations in only a few of the somatic submodality-specific groups. These include cells in the small-field and Pacinian cutaneous-responsive groups, excluding cells in the wide-field cutaneous-, muscle-, joint-, and noxious-responsive groups. Taken together these findings indicate that monoclonal antibody Cat-301 is capable of selectively identifying neurons with distinct functional properties in the mammalian somatosensory thalamus.     

Neuropeptide Y regulation of LHRH release in the median eminence: immunocytochemical and physiological evidence in hens

It has been suggested that hypothalamic median eminence (ME) might be a control site for luteinizing hormone-releasing hormone (LHRH) release. Thus, stimulatory and/or inhibitory inputs acting at this site might be involved in regulating LHRH release from the ME and, therefore, luteinizing hormone (LH) release from the anterior pituitary. Since a role for neuropeptide Y (NPY) on LH release has been suggested, we have hypothesized that NPY might act in the ME to control preovulatory LHRH release in hens. To examine this possibility we have determined: (a) the immunocytochemical distribution of LHRH and NPY in the ME of the hen, (b) the basal and NPY-stimulated release of LHRH in vitro from the ME of hens undergoing a natural or a premature preovulatory surge of LH, and (c) the tissue content of LHRH and NPY in microdissected MEs, at various times before and during a natural or a premature preovulatory surge of LH. A potential role for NPY on LHRH release in the ME is suggested for the following reasons. (a) There are opportunities for synaptic interactions between NPY and LHRH-containing axons at this site. LHRH-containing cell bodies localized in the anterior hypothalamus/medial preoptic area project to the ME. NPY-containing perikarya, concentrated in the ventromedial aspect of the arcuate nucleus, might contact LHRH processes going to the ME and/or might themselves send axons to the ME, (b) Addition of NPY to the incubation media increases LHRH release from microdissected ME tissue of hens killed at the time of the natural preovulatory surge of LH, but not in hens killed 7 h before the occurrence of this surge. However, the stimulatory effect of NPY on LHRH release can be induced at this latter time when a premature LH surge is elicited. While the natural preovulatory surge of LH occurs 4 h before the second ovulation in a sequence (C2 ovulation), administration of progesterone (P4) 10-14 h before the expected natural C2 ovulation advances the natural LH surge by 7-8 h. Thus, NPY might act as a physiological stimulus of LHRH release at the ME during the preovulatory surge of LH. This is suggested since in vitro basal LHRH release from denervated ME tissue does not change before and during the natural or the premature LH surge. Therefore, preovulatory release of LHRH in vivo might be under a continuous drive from stimulatory inputs to the LHRH neuron and NPY might be one of these stimulating factors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. 1985

The procedure currently used to diagnose infection in otitis externa has several limitations: it is slow to culture organisms on growth media, fungal infections are often missed, and extensive laboratory facilities and mycological expertise are required. A rapid, accurate and sensitive assay would greatly improve patient care by initiating appropriate antifungal treatment at the onset of disease. We report the development of a rapid detection assay for otomycosis using fungal-specific monoclonal antibodies to detect fungi in ear swabs by immunofluorescence microscopy. This assay could form the basis of a detection assay for fungal infections of the head and neck.     

Neuropeptide Y Y1-receptor stimulation is required for physiological amplification of preovulatory luteinizing hormone surges

Neuropeptide Y (NPY) has been shown to potentiate the actions of LHRH during the generation of preovulatory LH surges. It is not yet known, however, if activation of a specific subtype of NPY receptors in the anterior pituitary gland is an obligatory event in the stimulation of spontaneous LH surges. A battery of NPY receptor agonists, as well as the specific NPY Y1 receptor antagonist BIBP3226, were used to assess the role of Y1 receptors in the amplification of LH surges. In Exp 1, the potencies of a number of NPY agonists in facilitating LHRH-induced LH surges were assessed in pentobarbital (PB)-blocked, proestrous rats. The rank-ordered potencies of these compounds were determined to be PYY = [Leu31Pro34]NPY > NPY > hPP = rPP = NPY(13-36), which most closely reproduces the known rank-ordered affinties of these compounds for the Y1 receptor. In Exp 2, a Y1 subtype- specific antagonist, BIBP3226, was administered to unanesthetized, proestrous rats to assess the involvement of the Y1 receptor in the stimulation of spontaneous LH surges. The BIBP3226 compound strongly attenuated the endogenous proestrous LH surge, reducing the integrated value of LH secretion during the proestrous surge by more than 70%. In Exp 3, we assessed the ability of the Y1 receptor antagonist to block exogenous NPY effects on LHRH-induced LH surges. Treatment with BIBP3226 was found to completely prevent NPY amplification of LHRH-induced LH surges in pentobarbital-blocked, proestrous rats, thus confirming a pituitary locus of action of the drug. Taken together, these data clearly demonstrate that activation of neuropeptide Y receptors of the Y1 subtype is required for the physiological amplification of the spontaneous preovulatory LH surge in rats.