Postnatal intracerebroventricular exposure to neuropeptide Y causes weight loss in female adult rats

We investigated the effect of repetitive postnatal (2-7 days) intracerebroventricular administration of neuropeptide Y (NPY) on food intake and body weight gain in the 3- to 120-day-old Sprague-Dawley rats. NPY caused a 32% transient increase in body weight gain with elevated circulating insulin concentrations within 24 h. This early intervention led to the persistence of hyperinsulinemia and relative hyperleptinemia with euglycemia in the 120-day-old female alone. This perturbation was associated with 50% suppression in adult female hypothalamic NPY concentrations and a 50-85% decline in NPY immunoreactivity in the paraventricular and arcuate nuclei. This change was paralleled by a approximately 20% decline in food intake and body weight gain at 60 and 120 days. However, when exogenous NPY was stereotaxically reinjected into the paraventricular nucleus of the approximately 120-day-old adult females who were pretreated with NPY postnatally, an increase in food intake and body weight gain was noted, attesting to no disruption in the NPY end-organ responsivity. We conclude that postnatal intracerebroventricular NPY has long-lasting effects that predetermine the resultant adult phenotype in a sex-specific manner.     

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.     

Y2 receptors for neuropeptide Y in the nucleus of the solitary tract mediate depressor responses.

In anesthetized, spontaneously breathing rats, microinjections of selective agonists of neuropeptide Y (NPY) receptor subtypes were made into the medial region of the caudal nucleus of the solitary tract (NTS) at the level of the area postrema. This region of the rat NTS exhibits very high densities of NPY binding sites. Microinjections of the long C-terminal NPY fragment, NPY(13-36), a selective agonist at Y2 receptors, into the caudal NTS elicited pronounced, dose-related reductions in blood pressure and respiratory minute volume. Moreover, the specific pattern of cardiorespiratory responses elicited by NPY(13-36) was remarkably similar, over approximately the same dosage range, with the cardiorespiratory response pattern elicited by intact NPY. In contrast to the potent NTS-mediated responses evoked by NPY(13-36), similar microinjections conducted with either NPY(26-36), an inactive C-terminal NPY fragment, or [Leu31,Pro34]NPY, a NPY analog with specific agonist properties at Y1 receptors, into the same caudal NTS sites did not appreciably affect cardiorespiratory parameters even at 10-20-fold higher dosages. The present results with selective agonists for NPY receptor subtypes suggest that the depressor responses and reductions in minute volume elicited by microinjections of intact NPY and NPY(13-36) were mediated by Y2 receptors in the caudal NTS, likely distributed at presynaptic sites in the medial region of the subpostremal NTS.     

Attenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide Y

Neuropeptide Y (NPY) is a potent orexigenic peptide that is implicated in the feeding response to a variety of stimuli. The current studies employed mice lacking NPY (Npy−/−) and their wild-type (Npy+/+) littermates to investigate the role of this peptide in the feeding response to circadian and palatability cues. To investigate the response to a circadian stimulus, we assessed food intake during the 4-h period following dark onset, a time of day characterized by maximal rates of food consumption. Compared to Npy+/+ controls, intake of Npy−/− mice was reduced by 33% during this period (0.6 ± 0.1 g versus 0.9 ± 0.1 g; p ≤ 0.05). In contrast, intake did not differ between genotypes when measured over a 24-h period (3.7 ± 0.2 g versus 3.5 ± 0.3 g; p = ns). Furthermore, reduced dark cycle 4 h food intake in Npy−/− mice was not evident after a 24-h fast (1.4 ± 0.1 g for both genotypes; p = ns), despite a pronounced delay in the initiation of feeding (636 ± 133 s versus 162 ± 29 s; p ≤ 0.05). To investigate the role of NPY in the feeding response to palatability cues, mice were presented with a highly palatable diet (HP) for 1 h each day (in addition to having ad libitum access to chow) for 18 days. Npy+/+ mice rapidly increased daily HP intake such that by the end of the first week, they derived a substantial fraction of daily energy from this source (41 ± 3%). By comparison, HP intake was markedly reduced in Npy−/− mice during the first week (24 ± 7% of daily energy intake, p ≤ 0.05 versus Npy+/+), although it eventually increased (by Day 9) to values comparable to those of Npy+/+ controls. These experiments suggest that NPY contributes to the mechanism whereby food intake increases in response to circadian and palatability cues and that mechanisms driving food intake in response to these stimuli differ from those activated by energy restriction.     

Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

This study examines some of the cardiovascular and respiratory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in anaesthetised dogs. Intravenous injection of PACAP 27 caused an increase in arterial blood pressure and an increase in heart rate. The blood pressure response was significantly reduced by adrenoceptor blockade suggesting a mechanism of action mediated in part via catecholamines. The heart rate increase was unaltered by adrenoceptor blockade suggesting a direct effect of PACAP 27. PACAP 27 also caused potentiation of cardiac slowing caused by stimulation of the vagus nerve. In addition, PACAP 27 powerfully stimulated breathing. This was probably evoked by stimulation of arterial chemoreceptors, because bilateral section of the carotid sinus nerves abolished this effect. PACAP 27 had no effect on the ability of the cardiac sympathetic nerve to increase heart rate, nor on the interaction between the sympathetic and parasympathetic systems in the heart.     

Cardiorespiratory responses to HCl vs. lactic acid infusion

Previous reports indicate that intravenous infusion of HCl can alter breathing and blood pressure even if reductions in systemic arterial pH are prevented. To extend these findings, as well as to determine whether other acids elicit comparable results, this report compares the cardiopulmonary response between right atrial infusion of lactic acid and HCl in awake ponies. Lactic acid, infused at a dose of 1.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.062 and 0.092 U, respectively, and increased pulmonary arterial pressure (delta Ppa, 4 mmHg), heart rate (HR, 4/min), and tidal volume (delta VT, 190 ml/m2). HCl, infused at a reduced dose of 0.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.024 and 0.047 U, respectively, but produced increases in Ppa (delta 23 mmHg), HR (delta 42/min), and VT (delta 321 ml/m2) that were significantly greater than from the larger dose of lactic acid. These results indicate that cardiopulmonary responses to infusion acidosis differ between the type of acid infused. It is suggested that, in the unanesthetized pony, HCl-induced infusion acidosis has a unique cardiopulmonary-stimulating action unrelated to the pH changes imparted to the circulating arterial blood and that this response is absent during the infusion of lactic acid.     

Intracerebroventricular injection of neuropeptide Y modifies carbohydrate and lipid metabolism in chicks

The purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of neuropeptide Y (NPY) affects heat production (HP), body temperature, and plasma concentrations of metabolic fuels in chicks. ICV injection of NPY (0, 188 or 375 pmol) did not affect HP, but significantly lowered respiratory quotient as well as the rectal temperature. These data suggest that the energy sources for HP were modified by NPY in the body. This idea was confirmed by subsequent experiments in which ICV injection of NPY significantly reduced plasma glucose and triacylglycerol concentrations but increased non-esterified fatty acid concentrations. The effect of NPY on the utilization of metabolic fuels was not associated changes in plasma catecholamine and corticosterone concentrations. In summary, the present study demonstrated that central NPY modifies peripheral carbohydrate and lipid metabolism in chicks.     

Structure of neuropeptide Y dimer in solution.

The structure of porcine neuropeptide Y in 0.05 M CD3COOD/D2O was determined by nuclear magnetic resonance spectroscopy. Nuclear Overhauser spectra yielded 377 distances which define a helical segment formed by residues 11-36. An additional set of 24 distances were interpreted as intermolecular distances within a dimer. A combination of distance geometry calculations, energy minimization and molecular dynamics yielded a model of the dimer having antiparallel packing of two curved helical units whose hydrophobic sides form a well defined core. The N-terminus (residues 1-9) appears as an unstructured mobile segment. Large changes in the intrinsic fluorescence intensity of neuropeptide Y tyrosine residues allowed the determination of the dimer dissociation constant as 1.6 +/- 0.6 microM at pH 2-8 in aqueous buffers and also indicated the enclosure of several tyrosine residues in the hydrophobic environment of the interface region in the dimeric species. Fluorescence anisotropy data reveals the slow rotation of such shielded residues.     

去甲肾上腺素参与家兔脑室注射P物质的心血管效应

目的:深入探讨脑内注射SP的心血管效应及其与去甲肾上腺素能系统的关系.方法:家兔乌拉坦静脉麻醉,侧脑室注射SP或预先注射肾上腺素能受体阻断剂酚妥拉明、哌唑嗪、育亨宾.记录给药前后平均动脉血压(MAP)、左室收缩压(LVSP)、左心室收缩末期压(LVEDP)、室内压最大上升速率( dp/dtmax)和下降速率(-dp/dtmax)、心肌收缩成分实测最大缩短速度(Vpm)、心率(HR).观察脑室注射SP后小脑延髓池脑脊液中NA含量的变化.结果:①与对照组比较,icv SP可引起HR、LVSP、LVEDP、 dp/dtmax、-dp/dtmax和Vpm值明显增加(P<0.05),同时,小脑延髓池脑脊液中NA含量显著升高(P<0.05).②酚妥拉明或哌唑嗪预处理可显著减弱脑室注射SP引起心血管增强效应(P<0.05),但育亨宾预处理对注射SP引起的心血管效应无明显影响(P<0.05).结论:①脑内注射SP可增强心脏的收缩功能、升高动脉血压.②脑内α1肾上腺素能受体可能参与侧脑室注射SP的心血管增强效应.③中枢应用SP可促进NA能神经元释放NA或抑制突触前膜重摄取NA.这可能是脑内SP心血管效应的一个重要机制.     

Cardiorespiratory and neuromuscular responses to motocross riding

The aim of the present study was to examine physiological and neuromuscular responses during motocross riding at individual maximal speed together with the riding-induced changes in maximal isometric force production. Seven A-level (group A) and 5 hobby-class (group H) motocross-riders performed a 30-minute riding test on a motocross track and maximal muscle strength and oxygen uptake (VO2max) tests in a laboratory. During the riding the mean (+/-SD) VO2 reduced in group A from 86 +/- 10% to 69 +/- 6% of the maximum (P < 0.001), whereas in group H the corresponding reduction was from 94 +/- 25% to 82 +/- 20% (P < 0.05). This relative VO2 during the riding correlated with riding speed (r = 0.70, P < 0.01). Heart rate (HR) was maintained at the level of 97 +/- 7% of its maximum in group A and at 98 +/- 3% in group H. Mean muscle activation of the lower body during riding varied between 24% and 38% of its maximum in group A and between 40% and 45% in group H. In conclusion, motocross is a sport that causes great physical stress and demands on both skill and physical capacity of the rider. Physical stress occurs as the result of handling of the bike when receiving continuous impacts in the situation requiring both aerobic and anaerobic metabolism. Our data suggest that both maximal capacity and strain during the ride should be measured to analyze the true physiological and neuromuscular demands of motocross ride. For the practice, this study strongly suggests to train not only aerobic and anaerobic capacity but also to use strength and power training for successful motocross riding.     

Hypothalamic neuropeptide Y receptor characteristics and NPY-induced feeding responses in lean and obese Zucker rats.

Increased hypothalamic neuropeptide Y levels have previously been demonstrated in several hypothalamic nuclei of the (fa/fa) Zucker rat. This study set out to characterise hypothalamic NPY receptors in both genotypres and to study the effect of exogenous NPY on feeding behavior in these rats. Spontaneous daytime food intake was raised in the obese rat (p less than 0.05). Total hypothalamic receptor density (Bmax) was reduced in the obese rat compared with the lean rat (by 56%, p less than 0.005), but affinity remained unaltered. The lowest dose of NPY tested (23.5 pmol) stimulated daytime feeding in lean rats after 1, 2 and 3 hours but was inaffective in the obese rat (p less than 0.05). At two higher doses (235 pmol and 2.35 nmol), NPY was equipotent in both genotypes over 1 and 2 hours but NPY-induced feeding was attenuated over 3 hours in the obese rat. These results suggest an overactive endogenous NPYergic system in the obese (fa/fa) rat which might contribute to hyperphagia and obesity in this strain.     

Cardiorespiratory responses of white sturgeon to environmental hypercapnia

Cardioventilatory variables and blood-gas, acid-base status were measured in cannulated white sturgeon (Acipenser transmontanus) maintained at 19 degrees C during normocapnic and hypercapnic (Pw(CO(2)) approximately 20 Torr) water conditions and after the injection of adrenergic analogs. Hypercapnia produced significant increases in arterial PCO(2), ventilatory frequency, and plasma concentration of cortisol and epinephrine, and it produced significant decreases in arterial pH and plasma concentration of glucose but no change in arterial PO(2), hematocrit, and concentration of lactate or norepinephrine. Hypercapnia significantly increased cardiac output (Q) by 22%, mean arterial pressure (MAP) by 8%, and heart rate (HR) by 8%. However, gut blood flow (GBF) remained constant. In normocapnic fish, phenylephrine significantly constricted the splanchnic circulation, whereas isoproterenol significantly increased Q and produced a systemic vasodilation. During hypercapnia, propranolol significantly decreased Q, GBF, MAP, and HR, whereas phentolamine significantly decreased MAP and increased GBF. These changes suggest that cardiovascular function in the white sturgeon is sensitive to both alpha- and beta-adrenergic modulation. We found microspheres to be unreliable in predicting GBF on the basis of our comparisons with simultaneous direct measurements of GBF. Overall, our results demonstrate that environmental hypercapnia (e.g., as is experienced in high-intensity culture situations) elicits stress responses in white sturgeon that significantly elevate steady-state cardiovascular and ventilatory activity levels.