Administration Of Neuropeptide Y Research Articles

Neuropeptide Y modulates pituitary–adrenal axis activity in the lizard, Podarcis sicula

The role of neuropeptide Y (NPY) in the modulation of the pituitary–adrenal axis activity in a lizard, Podarcis sicula, was investigated by in vivo NPY administration. The effects were evaluated by examination of the morphological and morphometrical features of the tissues as well as the plasma levels of ACTH, corticosterone, aldosterone, norepinephrine, and epinephrine. Intraperitoneally administered NPY (27 nmol /100 g body wt) raised ACTH plasma levels (from 5.23 ± 0.06 pg/ml in carrier injected specimens to 6.83 ± 0.01 pg/ml, 24 h after the injection). In the steroidogenic cells a strong decrease of lipid amount was found; corticosterone plasma level increased from 6.28 ± 0.02 ng/ml in carrier injected lizards to 7.96 ± 0.01 ng/ml 24 h after the injection); aldosterone levels were raised from 1.88 ± 0.02 ng/ml in carrier injected specimens to 6.38 ± 0.05 ng/ml 24 h after the experimental treatment. In the chromaffin tissue, an increase in the number of epinephrine cells and a decrease in the number of norepinephrine cells were observed, decreasing the numeric norepinephrine/epinephrine (NE/E) cell ratio, from 1.4/1 of control specimens to 0.5/1 24 h after NPY administration. Moreover, norepinephrine plasma level were elevated from 922 ± 4.30 pg/ml in carrier injected specimens to 3075 ± 11.30 pg/ml 24 h after NPY administration; epinephrine plasma level increased from 502 ± 2.40 pg/ml in carrier injected specimens to 2759 ± 8.70 pg/ml 24 h after the experimental treatment. Consistent with these findings, morphological observations showed many chromaffin cells weakly stained and with a reduced content of secretory granules. These results suggest that, in P. sicula, NPY may play a role in the modulation of the pituitary–adrenal axis activity. Previous studies localized NPY in the epinephrine cells of P. sicula adrenal gland; taken together, these results suggest that this peptide might participate in the regulation of adrenal gland activity, enhancing corticosteroid and catecholamine secretion in a paracrine/autocrine manner. The mechanism of action of NPY is discussed.

Estrogen-induced mu-opioid receptor internalization in the medial preoptic nucleus is mediated via neuropeptide Y-Y1 receptor activation in the arcuate nucleus of female rats.

The endogenous peptides beta-endorphin (beta-END) and neuropeptide Y (NPY) have been implicated in regulating sexual receptivity. Both beta-END and NPY systems are activated by estrogen and inhibit female sexual receptivity. The initial estrogen-induced sexual nonreceptivity is correlated with the activation and internalization of mu-opioid receptors (MORs), in the medial preoptic nucleus (MPN). Progesterone reverses the estrogen-induced activation/internalization of MOR and induces the sexual receptive behavior lordosis. To determine whether NPY and endogenous opioids interact, we tested the hypothesis that estrogen-induced MOR activation is mediated through NPY-Y1 receptor (Y1R) activation. Retrograde tract tracing demonstrated Y1Ron beta-END neurons that projected to the MPN. Sex steroid modulation of MOR in the MPN acts through NPY and the Y1R. Estradiol administration or intracerebroventricular injection of NPY activated/internalized Y1R in the arcuate nucleus and MOR in the MPN of ovariectomized (OVX) rats. Moreover, the selective Y1R agonist [Leu31, Pro34]-Neuropeptide Y (LPNY) internalized MOR in the MPN of OVX rats. The Y1R antagonist (Cys31, Nva34)-Neuropeptide Y (27-36)2 prevented estrogen-induced Y1R and MOR activation/internalization. NPY reversed the progesterone blockade of estradiol-induced Y1R and MOR internalization in the arcuate nucleus and MPN, respectively. Behaviorally, LPNY inhibited estrogen plus progesterone-induced lordosis, and the MOR-selective antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr amide reversed LPNY-induced inhibition of lordosis. These results suggest that a sequential sex steroid activation of NPY and MOR circuits regulates sexual receptivity.

The Y 1 receptor subtype mediates the cardiovascular changes evoked by NPY administered into the posterior hypothalamic nucleus of conscious rat

An earlier study showed that the neuropeptide Y (NPY) receptor antagonist PYX-2 blocks the enhancement of a carbachol (CCh)-evoked pressor response produced by prior NPY administration into the posterior hypothalamic nucleus (PHN). The Y receptor subtype that mediates this response, and an increase in mean arterial pressure (MAP) and heart rate, remained unknown due to the lack of selectivity of PYX-2 for the Y receptor subtypes. Thus, the present study was undertaken to elucidate the Y receptor subtype responsible for mediating the NPY-evoked cardiovascular responses from the PHN by determining the rank order of potency of several NPY-related peptides for increasing MAP, and by correlating the pressor response evoked by these peptides to reported K i's and IC 50's for the Y 1, Y 2, Y 4 and Y 5 receptor subtypes. The pharmacological profile (PYY≥NPY≥[Leu 31,Pro 34]NPY≥NPY 13–36≥hPP) and correlations suggest that the Y 1 and/or Y 5 receptor subtypes mediate these cardiovascular changes. Administration of the relatively non-selective Y receptor antagonist PYX-2 or the selective Y 1 receptor antagonist BIBP 3226 into the PHN prior to NPY completely blocked the cardiovascular responses. BIBP 3226 also blocked the cardiovascular changes evoked by [Leu 31,Pro 34]NPY, NPY 13–36 and human pancreatic polypeptide (hPP). In contrast, neither BIBP 3226 nor PYX-2 inhibited the cardiovascular changes induced by peptide YY (PYY) or CCh microinjection into the PHN. These results show that NPY and PYY act on different receptors to mediate their respective cardiovascular changes from the PHN with NPY stimulating the Y 1 receptor.

Neuropeptide Y alters stress‐induced changes in trace element concentrations of brain in chronically immobilized rats

AbstractCentral administration of neuropeptide Y (NPY) produces anxiolytic‐like behavioral responses in the conflict test, elevated plus maze, fear‐potentiated startle paradigm, and in the chronic immobilization stress. Exogenously administrated NPY also protects against the anxiogenic effects of corticotropin‐releasing factor. In the present study, we aimed to determine the effects of centrally administered NPY on the trace element disturbances in brain tissues (frontal and temporal lobes and brain stem) and the other major organs including liver, spleen (zinc [Zn]‐, copper [Cu]‐, and iron‐rich tissues), kidney, and stomach in chronically immobilized rats. The immobilization stress was performed in special cages in which the animals were not able to move. The rats in chronic stress and chronic stress + NPY groups were kept in the cages daily for 7 min for 15 consecutive days. Intracerebroventricular (ICV) cannulas were placed to the right lateral ventricles of the rats by using stereotaxic method. In the control and chronic stress groups, 5 μL of saline (NaCl 0.9%), and in the chronic stress + NPY group, 8 μg NPY/5 μL saline solutions, were administered into the brain via ICV cannula, respectively. Controls and immobilized rats were decapitated 30 min after the injections were over and samples of tissue were taken. Zn, Cu, and iron levels of the frontal lobe, temporal lobe, brain stem, liver, spleen, kidney, and stomach were determined by flame atomic absorption spectrophotometer. Zn and Cu levels were significantly increased in the frontal lobe, temporal lobe, and brain stem in response to chronic immobilization stress daily for 7 min for 15 consecutive days. The administration of NPY inhibited the elevation of Zn in these three parts of brain but did not affect the elevation of Cu in the frontal lobe and brain stem. Increases in Zn and Cu levels of frontal, temporal lobes, and brain stem may be related to induction of MT‐I mRNA expression by chronic immobilization stress, and NPY may affect this induction of MT‐I, altering corticotropin‐releasing factor release in the stress conditions. J. Trace Elem. Exp. Med. 17:283–290, 2004. © 2004 Wiley‐Liss, Inc.

Appetite regulation: from the gut to the hypothalamus.

these proportions had increased to 26% and 22%, respectively, with 55% of women and 66% of men being overweight (BMI > 25 kg/m 2 ; Health Survey for England, 2001), reflecting a worldwide trend which is most marked in, but not restricted to, the developed world. Most of us in affluent countries live in a privileged land of plenty where high calorie foods are easily available and in which we have a limited need for exercise. The rising prevalence of obesity in children is of particular concern (Chinn & Rona, 2001).

Regulation of intestinal and hypothalamic apolipoprotein A-IV.

This review discusses the regulation of the intestinal and hypothalamic apolipoprotein A-IV (apo A-IV) gene and protein expression. Apo A-IV is a glycoprotein secreted together with triglyceride-rich lipoproteins by the small intestine. Intestinal apo A-IV synthesis is stimulated by fat absorption, probably mediated by chylomicron formation. This stimulation of intestinal apo A-IV synthesis is attenuated by intravenous leptin infusion. Chronic ingestion of a high-fat diet blunts the intestinal apo A-IV in response to dietary lipid. Intestinal apo A-IV synthesis is also stimulated by members of the pancreatic polypeptide family, including peptide YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP). Recently, apo A-IV was demonstrated to be present in the hypothalamus as well. Hypothalamic apo A-IV level was reduced by food deprivation and restored by lipid feeding. Intracerebroventricular administration of apo A-IV antiserum stimulated feeding and decreased the hypothalamic apo A-IV mRNA level, implying that feeding is intimately regulated by endogenous hypothalamic apo A-IV. Central administration of NPY significantly increased hypothalamic apo A-IV mRNA levels in a dose-dependent manner.

Alpha adrenergic receptors are involved in the contractile activity of neuropeptide Y in the porcine isolated ovarian artery

The objective of this study was to determine whether α-adrenergic receptors are involved in the contractile activity of neuropeptide Y (NPY) in the porcine isolated ovarian artery collected from immature pigs and from the animals on day 1–5, 8–13 and 17–20 of the estrous cycle. NPY increased (P < 0.05) blood pressure in preparations collected form the immature and mature pigs. NPY administration into prazosin pre-treated vessels increased (P < 0.05) blood pressure in preparations of the immature and mature animals with the highest potency in the vessels from days 17–20 of the cycle. Simultaneous methoxamine and NPY treatment caused an increase (P < 0.05) in blood pressure in the vessels from all the periods examined with the highest potency in the preparations from days 17–20 of the cycle. NPY administration at the time of the maximum response to rauwolscine increased (P < 0.05) blood pressure in the preparations from the immature and mature pigs with the highest changes in the preparations from days 17–20 of the cycle. In clonidine pre-treated ovarian arteries, NPY insignificantly increased (P > 0.05) blood pressure in the preparations collected from the immature pigs and on days 1–5, 8–13 of the cycle, and significantly increased (P < 0.05) blood pressure in preparations from the animals on days 17–20 of the oestrous cycle. The present study has revealed that NPY increases blood pressure in the isolated porcine ovarian artery and that α-adrenergic receptors are involved in the vosocontractile action of this peptide. Moreover, the changes in the blood pressure caused by NPY alone or administered after α-adrenergic receptor agonists or antagonists treatment are dependent on steroid hormone concentrations.

Altered responses to orexigenic (AGRP, MCH) and anorexigenic (alpha-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats.

Food intake and energy expenditure are regulated by neuropeptides in the hypothalamus. While cocaine- and amphetamine-regulated transcript (CART) peptide and melanocortins such as alpha-melanocyte-stimulating hormone (alpha-MSH) are anorexigenic and increase energy expenditure, the endogenous melanocortin receptor antagonist agouti gene-related protein (AGRP), melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic, anabolic peptides. Alterations in the regulatory balance may promote excessive weight gain. The action of these peptides on paraventricular hypothalamic neurons was studied in brain slices of overweight, adult rats previously subjected to early postnatal overfeeding in small litters of only three pups per mother, compared to 12 pups per dam in control litters. CART, melanocortins and NPY significantly excited paraventricular neurons of controls, whereas neurons of small-litter rats were mainly inhibited. Inhibition was dominant following administration of AGRP, MCH and NPY. The altered responses of paraventricular neurons in adult small-litter rats might reflect a general mechanism of neurochemical plasticity and 'malprogramming' of hypothalamic neuropeptidergic systems acquired during the postnatal critical differentiation period, thus leading to permanently altered function of these regulatory systems of body weight.

Behavioral effects of neuropeptide Y in F344 rat substrains with a reduced dipeptidyl-peptidase IV activity

Dipeptidyl-peptidase IV (DPPIV/CD26) is involved in several physiological functions by cleavage of dipeptides with a Xaa-Pro or Xaa-Ala sequence of regulatory peptides such as neuropeptide Y (NPY). Cleavage of NPY by DPPIV results in NPY 3-36, which lacks affinity for the Y 1 but not for other NPY receptor subtypes. Among other effects, the NPY Y 1 receptor mediates anxiolytic-like effects of NPY. In previous studies with F344 rat substrains lacking endogenous DPPIV-like activity we found a reduced behavioral stress response, which might be due to a differential degradation of NPY. Here we tested this hypothesis and administered intracerebroventricularly two different doses of NPY (0.0, 0.2, 1.0 nmol) in mutant and wildtype-like F344 substrains. NPY dose-dependently stimulated food intake and feeding motivation, decreased motor activity in the plus maze and social interaction test, and exerted anxiolytic-like effects. More important for the present hypothesis, NPY administration was found to be more potent in the DPPIV-negative substrains in exerting anxiolytic-like effects (increased social interaction time in the social interaction test) and sedative-like effects (decreased motor activity in the elevated plus maze). These data demonstrate for the first time a differential potency of NPY in DPPIV-deficient rats and suggest a changed receptor-specificity of NPY, which may result from a differential degradation of NPY in this genetic model of DPPIV deficiency. Overall, these results provide direct evidence that NPY-mediated effects in the central nervous system are modulated by DPPIV-like enzymatic activity.

Time-dependent effects of neuropeptide Y infusion in the paraventricular hypothalamus on ingestive and associated behaviors in rats

In this study the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the daily regulation of feeding, drinking, locomotor activity, and nestbox occupation was investigated. These behaviors were recorded during and after bilateral infusion of NPY into the PVN of rats during the early (E) or late (L) part of the light phase. Administration of NPY caused a significant increase in feeding behavior at E, but not at L. In contrast to the feeding at E, L feeding was associated with increased water intake following NPY infusion. While locomotor activity was similar in sCSF- and NPY-infused rats at all times of the daily cycle, administration of NPY at L, but not at E increased nestbox occupation during the first few hours of the dark phase. This increased nestbox occupation was not associated with altered food intake or drinking behavior, implying that NPY-treated rats made frequent excursions between nestbox and food hopper/water bottle. Thus, feeding-associated drinking and explorative behavior are time-dependently modulated by NPY in the PVN, independent of locomotor activity.

Effects of Neuropeptide Y on Sucrose and Ethanol Intake and on Anxiety‐Like Behavior in High Alcohol Drinking (HAD) and Low Alcohol Drinking (LAD) Rats

Background: In a previous study, neuropeptide Y (NPY) administered into the lateral ventricles decreased ethanol intake in alcohol‐preferring (P) rats but not in alcohol‐nonpreferring (NP) or unselected Wistar rats. The purpose of the present investigation is to extend these findings in selectively‐bred high‐alcohol‐drinking (HAD)1 and low‐alcohol‐drinking (LAD)1 rats by examining the effects of intracerebroventricularly administered NPY on the elevated plus maze test of anxiety and on ethanol and sucrose intake.Methods: Female HAD1 and LAD1 rats were surgically implanted with cannula into the lateral ventricle. Following recovery, a test of anxiety was conducted in which the rats (n= 12–13/group) received either artificial cerebrospinal fluid (aCSF) or NPY (10 μg) 10 min prior to a 5‐min test on an elevated plus maze. Following anxiety testing, 11 HAD and 11 LAD rats were trained to self‐administer ethanol (8% w/v), and 5 HAD and 8 LAD rats were trained to self‐administer sucrose (2.5%) during daily 2‐hr sessions. A within‐subject design was used in which the rats were pretreated once a week with aCSF, 5 μg NPY, or 10 μg NPY prior to the drinking sessions.Results: HAD and LAD rats treated with aCSF did not differ in time spent in open arms of the plus maze. NPY increased time spent on the open arms to similar degrees in both rat lines. HAD rats consumed more ethanol and sucrose than LAD rats. NPY increased sucrose intake in both rat lines. However, the same doses of NPY reduced ethanol intake in HAD but not in LAD rats.Conclusion: The plus maze results indicated that selective breeding for high and low alcohol preference in the HAD1 and LAD1 rats, respectively, did not yield differences in anxiety‐like behavior and in response to the anxiolytic effects of NPY. The increases in sucrose intake were consistent with the known orexigenic effects of NPY. The decreased ethanol intake following NPY administration in HAD rats was similar to previous observations with P rats and is consistent with the hypothesis that ethanol intake and NPY activity may be inversely related.

Attenuation of circadian light induced phase advances and delays by neuropeptide y and a neuropeptide y y1/y5 receptor agonist

Circadian rhythms can be synchronised to photic and non-photic stimuli. The circadian clock, anatomically defined as the suprachiasmatic nucleus in mammals, can be phase shifted by light during the night. Non-photic stimuli reset the circadian rhythm during the day. Photic and non-photic stimuli have been shown to interact during the day and night. Precise mechanisms for these complex interactions are unknown. A possible pathway for non-photic resetting of the clock is thought to generate from the intergeniculate leaflet, which conveys information to the suprachiasmatic nucleus (SCN) through the geniculohypothalamic tract and utilises neuropeptide Y (NPY) as its primary neurotransmitter. Interactions between light and NPY were investigated during the early (2 h after activity onset) and late (6 h after activity onset) night in male Syrian hamsters. NPY microinjections into the region of the SCN significantly attenuated light-induced phase delay, during the early subjective night. Phase advances to light were completely inhibited by the administration of NPY during the late night. The precise mechanism by which NPY attenuates or blocks photic phase shifts is unclear, but the NPY Y5 receptor has been implicated in the mediation of this inhibitory effect. The NPY Y1/Y5 receptor agonist, [Leu 31,Pro 34]NPY, was administered via cannula microinjections following light exposure during the early and late night. [Leu 31,Pro 34]NPY significantly attenuated phase delays to light during the early night and blocked phase advances during the late night, in a manner similar to NPY. These results show the ability of NPY to attenuate phase shifts to light during the early night and block light-induced phase advances during the late night. Furthermore, this is the first in vivo study implicating the involvement of the NPY Y1/Y5 receptors in the complex interaction of photic and non-photic stimuli during the night. The alteration of photic phase shifts by NPY may influence photic entrainment within the circadian system.

Intracerebroventricular administration of NPY stimulates resistin gene expression in mice

Resistin is thought to cause insulin resistance and link obesity to type 2 diabetes mellitus. However, little is known about the effects of neuropeptide Y (NPY) on resistin gene expression in white adipose tissue (WAT). Resistin gene expression was determined by northern blot analysis in food-deprived mice after NPY administration. Administered NPY (1 nmol/mouse) significantly increased resistin mRNA expression in WAT by 72% compared with artificial cerebrospinal fluid treated controls. These observations indicate that NPY might have a role in regulating resistin gene expression in WAT and that the novel brain-fat axis might be involved in the pathogenesis of obesity and related diseases.

Fasting activates neuropeptide Y neurons in the arcuate nucleus and the paraventricular nucleus in the rhesus macaque

It is well accepted that neuropeptide Y (NPY) plays a pivotal role in the regulation of food intake and energy homeostasis in the rodent, with NPY neurons in the arcuate nucleus (ARH) being thought of as the major contributor to the complex central feeding circuitry. Recent data from our group also indicate that NPY is important in the regulation of energy homeostasis in the nonhuman primate (NHP); exogenous NPY administration into the 3rd ventricle is a potent stimulator of food intake in the male rhesus macaque. The purpose of this study was to determine if NPY neurons in the rhesus macaque respond to a metabolic challenge, induced by 48 h of fasting, in a manner similar to that seen in the rodent. NPY mRNA was detected in hypothalamic sections from 48-h fasted or fed rhesus monkeys by in situ hybridization, using a [ 35S]UTP-labeled riboprobe specific for human NPY. Not surprisingly, NPY mRNA was abundant in the ARH of the NHP; however, of great interest was the expression of NPY mRNA in neurons within the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). This raised the question as to whether all of these populations of NPY neurons are sensitive to changes in energy availability. Indeed, NPY expression in the ARH and PVH was significantly elevated in response to fasting; however, no significant change was detected in the SON. These data indicate that the NPY neurocircuitry involved in the regulation of food intake is more complex in the NHP than in rodents.

Neuropeptide Y and lipid increase apolipoprotein AIV gene expression in rat hypothalamus

Apolipoprotein AIV (apo AIV) is a circulating signal released from intestinal cells in response to lipid feeding and contributes to the anorectic effect of a lipid meal. We have demonstrated that apo AIV is also synthesized in the hypothalamus, and that hypothalamic apo AIV gene expression is regulated physiologically. Neuropeptide Y (NPY) is a hypothalamic neuropeptide with broad regulatory actions in the central nervous system. In the present studies, the effects of intracerebroventricular (i.v.t.) administration of NPY and of intraduodenal lipid infusion on hypothalamic apo AIV gene expression were determined using competitive RT-PCR in fasted rats. I.v.t. injection of NPY alone significantly increased apo AIV mRNA levels in the hypothalamus in a dose-dependent manner. Intraduodenal infusion of lipid also stimulated the gene expression of hypothalamic apo AIV, but no further significant increment occurred when i.v.t. injection of NPY was combined with lipid infusion. These results suggest that NPY and lipid may regulate apo AIV gene expression in the rat hypothalamus.

GnRH-LH secreting cells axis in the pituitary of the teleost Clarias batrachus responds to neuropeptide Y treatment: an immunocytochemical study

An attempt has been made to immunocytochemically visualize the effect of neuropeptide Y (NPY) on the GnRH fibers and luteinizing hormone (LH) secreting cells in the pituitary of the catfish, Clarias batrachus. Two hours following the intracranial administration of NPY at the dose of 20 ng/g body wt, a significant increase in the area occupied by the GnRH-like immunoreactive fibers, and population and size of the LH cells was observed. The treatment also resulted in considerable augmentation of immunoreactivity in the LH cells. Double immunolabeling revealed NPY fibers directly terminating on the LH cells. The results suggest that NPY may (a) stimulate some GnRH containing hypophysiotropic neuronal group in the brain, (b) promote anterograde transport of GnRH to the pituitary gland, and (c) up-regulate the LH cells.

Attenuation of phase shifts to light by activity or neuropeptide Y: a time course study

Circadian rhythms in mammals can be synchronised to photic and non-photic stimuli. Interactions between photic and behavioural stimuli were investigated during the late subjective night, 6 h after activity onset in Syrian hamsters (CT18). Light pulses of 130 lx for 15 min at this time resulted in phase advance shifts. Novel wheel exposure, for a period of 3 h, following photic stimulation was able to attenuate the phase advancing effects of light. A time delay of up to 60 min between photic and behavioural stimuli also resulted in significant attenuation of light-induced phase shifts ( P<0.05). A 90-min interval between stimuli resulted in no significant attenuation. Novel wheel exposure mediates its effects via the intergeniculate leaflet, which conveys information to the SCN and utilises neuropeptide Y (NPY) as its primary neurotransmitter. Phase shifts to light pulses given at CT18 were attenuated by NPY administration. Neuropeptide Y injections up to 60 min post-light exposure significantly attenuated phase shifts by 50% on average. However a 90-min interval between light and NPY microinjection did not significantly affect light-induced phase shifts. These results confirm previous work indicating that novel wheel exposure and NPY administration can modulate light-induced phase shifts during the late night. Further, they show for the first time that the time course for this interaction is similar between wheel running and NPY. Most significantly, our work indicates that the time course in vivo in the late night is similar to that shown previously in vitro during the early night.

Luteinizing hormone and growth hormone secretion in ewes infused intracerebroventricularly with neuropeptide Y

Neuropeptide Y (NPY) provides an important hypothalamic link between nutritional status and neuroendocrine mechanisms regulating growth and reproduction. The objective of the following series of experiments was to determine the effects of single or continuous administration of NPY on secretion of luteinizing hormone (LH) and (or) growth hormone (GH). In experiment 1, four ovariectomized (OVX) ewes and four OVX+estrogen-treated ewes each received, in a 4×4 Latin Square arrangement of treatments, a single injection of 0, 0.5, 5, or 50 μg NPY via an intracerebroventricular (i.c.v.) cannulae to determine the effects on secretion of GH. NPY significantly elevated serum GH at the 50 μg dose regardless of estrogen exposure ( P=0.003). In experiment 2, eight OVX ewes were infused i.c.v. with NPY or saline ( n=4/trmt) continuously for 20 h in a linearly increasing dose, ending at 50 μg/h NPY. Blood samples were collected via jugular cannulae every 10 min during hour –4–0 (interval 1, pre-treatment), hour 6–10 (interval 2) and hour 16–20 (interval 3) relative to the initiation of infusion (0 h). Mean LH and LH pulse frequency were lower in NPY- versus saline-infused ewes during intervals 2 and 3 ( P<0.01), but NPY had no discernable effect on serum GH ( P>0.10). In experiment 3, four OVX ewes were continuously infused with NPY as in experiment 2, except that the maximum 50 μg/h dose was achieved after only 10 h of infusion. Blood samples were collected every 10 min, beginning 4 h before and continuing until 4 h after the NPY infusion. Mean serum LH changed significantly over time ( P=0.0001), decreasing below pre-treatment levels by hour 3 of NPY infusion ( P<0.01), and returning to pre-treatment concentrations following the end of infusion ( P>0.15). Serum GH also changed significantly over time ( P<0.001). Mean GH levels tended to be greater than pre-treatment levels by hour 2 of infusion ( P<0.08), but thereafter returned to basal levels. Serum GH also increased following the end of NPY infusion ( P<0.03). From these data we conclude that NPY exerts a persistent inhibitory effect on secretion of LH, and may stimulate the secretion of GH during the initiation and cessation of infusion of NPY. These observations support a role for NPY in mediating the effects of undernutrition on both LH and GH, and also provide evidence for potential mechanisms by which leptin, acting through NPY, may stimulate the secretion of GH.

Plasma Neuropeptide Y Concentrations in Patients on Hemodialysis

Background: Neuropeptide Y (NPY) is a 36-amino-acid peptide that was originally isolated from the porcine brain. NPY, in contrast to leptin, is one of the most potent appetite stimulants. In some previous studies, NPY was found to be correlated with mean blood pressure (MBP) and fluid volume in patients on hemodialysis (HD), contributing to volume-induced hypertension. However, it is still unclear which NPY-sensitive neuronal pathways are responsible for the various changes seen in response to central NPY administration. In this study we analyzed the correlation of circulating levels of NPY with parameters of nutritional conditions, and we investigated the relationships between NPY concentrations and clinical markers of fluid volume in patients on HD. We also evaluated the effects of high-flux dialysis membranes on plasma NPY levels as compared with those of low-flux membrane. Methods: Plasma NPY concentrations in patients on regular HD were measured using commercially available radioimmunoassay (RIA) kits. We examined the relationship between plasma NPY concentration and other clinical indices in patients on HD. Results: Plasma NPY concentrations were inversely correlated with the serum urea nitrogen levels (r = –0.32) as well as protein catabolic rate (PCR) (r = –0.28). Plasma NPY was also correlated with the increase in body weight between HD sessions (r = 0.29). On the other hand, plasma NPY concentrations were not correlated with MBP, atrial natriuretic peptide (ANP), or adrenomedullin (AM). The reduction rate of plasma NPY with a high-flux dialysis membrane was significantly higher than that with a low-flux dialysis membrane. Conclusions: The secretion of NPY may be enhanced in a poor state of nourishment and stress induced by fluid volume overload in patients on HD, and plasma NPY is removed by a high-flux dialyzer.

Neuropeptide Y administration into the amygdala does not affect ethanol consumption

Evidence seems to indicate that the anxiolytic effects of centrally administered neuropeptide Y (NPY) are mediated by the central nucleus of the amygdala. Because findings seem to indicate that ethanol may be self-administered partially for its anxiolytic effects, it was hypothesized that NPY, microinjected into the central nucleus of the amygdala, would decrease ethanol intake. In this study, we examined the effects of NPY, administered into the central nucleus of the amygdala, on ethanol, sucrose, and food consumption, as well as the concomitant effects of NPY on cortical electroencephalographic activity. Wistar rats were implanted with cortical recording electrodes and cannulae above the central amygdaloid nuclei, after use of a sucrose-substitution procedure, to establish ethanol self-administration. Neuropeptide Y (0–250 pmol/0.5 μl) was infused into the amygdala before drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), or food was available. Consumption, locomotor activity, and cortical electroencephalographic activity were then monitored concurrently. Neuropeptide Y had no effect on the intake of 10E, 2S, or food, nor on the cortical electroencephalographic or locomotor activity. However, as reported previously, distinct changes in the electroencephalogram were associated with consumption of ethanol and sucrose. Cortical power in the 6–8 Hz frequency range was significantly increased during the beginning of the sucrose and ethanol sessions, with greater increases observed during the sucrose session. Overall, these findings support the suggestion that NPY administration into the central nucleus of the amygdala does not alter consumption of 10E, 2S, or food, nor the cortical electroencephalographic or locomotor activity.