Takashi Bungo

Intracerebroventricular injection of orexins does not stimulate food intake in neonatal chicks

1. Recently, 2 novel neuropeptides were discovered, both derived from the same precursor by proteolytic processing, which bind and activate 2 closely related orphan G protein-coupled receptors, Named orexin-A and -B (Sakurai et al., 1998). Both stimulate food intake when administered centrally to rats. 2. Our aim was to elucidate whether central injection of mammalian orexin-A or -B stimulates food intake in the chick. 3. Under conditions of free access to food, orexin-A did not alter the food intake of chicks, but cumulative food intake was significantly suppressed by orexin-B. 4. The orexin-B was then administered to chicks deprived of food for 3 h to confirm its suppressive effect. No significant effect of orexin-B on food intake was detected. 5. Central injection of orexin-B did not modify food intake when appetite was stimulated by fasting. 6. Neither of these orexins appears to stimulate feeding in chicks.

Central administration of α-melanocyte stimulating hormone inhibits fasting- and neuropeptide Y-induced feeding in neonatal chicks

In the present study, the effect of intracerebroventricular (i.c.v.) administration of alpha-melanocyte stimulating hormone (alpha-MSH) on food intake of neonatal chicks was examined. In experiment 1, i.c. v. injection of alpha-MSH (0.04, 0.2 and 1 microg) significantly inhibited food intake of 3-h fasted chicks in a dose-dependent manner. In experiment 2, alpha-MSH strongly inhibited neuropeptide Y-induced feeding when neuropeptide Y (2.5 microg) and several doses of alpha-MSH were given simultaneously i.c.v. These results suggest that alpha-MSH plays an important role in the regulation of food intake of neonatal chicks.

Intracerebroventricular administration of mouse leptin does not reduce food intake in the chicken

Recently, it has been suggested that leptin plays an important role in regulation of food intake and metabolism in rats and mice, however, the effect of central administration of leptin on food intake in chicks has not been reported. We have investigated the anorexigenic effect of leptin administered by intracerebroventricular (i.c.v.) injection in chicks using mouse leptin, which shows 97% homology to chicken leptin. Three experiments were conducted. After being deprived of food for 3 h, male broiler chicks were administered leptin by i.c.v. injection at dose levels of 0, 0.2, 1.0 and 5.0 microg (Experiment 1) or 0, 2.5 and 5.0 microg (Experiment 2). The birds were allowed free access to the diet for 2 h (Experiment 1) and 24 h (Experiment 2) after treatment. Male Single Comb White Leghorn chicks were used in Experiment 3 and were treated in the same manner as in Experiment 1. In all experiments, central administration of mouse leptin did not influence food intake in the time periods examined. It appears that either mouse leptin does not bind to the chicken leptin receptor or in the chicken brain the leptin receptor may be absent.

Relationships between feeding and locomotion behaviors after central administration of CRF in chicks

The effect of intracerebroventricular injection of corticotropin-releasing factor (CRF) on various behaviors in chicks was determined at 15-min intervals over a 30-min period. Food intake of chicks was significantly decreased, and pecking rhythm was significantly delayed by CRF during the first 15-min post-injection. The similar tendencies were observed in the second 15-min post-injection, but not significantly different. Stepping, as an indicator of locomotion, was not different at 15-min post-injection, but was increased by CRF, thereafter. These results suggest that CRF acts within the central nervous system to decrease food intake and increase locomotion in the chick.

Chicken leptin receptor is functional in activating JAK-STATpathway in vitro.

Leptin is a cytokine-like hormone that regulates food intake and energy homeostasis via its interaction with the leptin receptor (LEPR) located in the target tissues. Leptin-dependent signal transduction pathways have been well characterised in mammals but less is known about them in other vertebrates. In birds, although the existence of the LEPR has been confirmed, the identity of the natural ligand for the LEPR is controversial and the signalling cascade is not fully understood either. Here, we describe the in vitro expression of chicken LEPR (chLEPR), which can mediate the leptin signal. Murine leptin specifically bound with the chLEPR, which initiated the activation of luciferase in chLEPR-expressing cells. Leptin stimulation led to phosphorylation of signal transducers and activators of transcription 3 (STAT3) via chLEPR, and Janus kinase(-2) (JAK(-2)) inhibitor partially blocked leptin-induced luciferase activation in CHO-K1 cells stably expressing chLEPR (CHO-chLEPR). RNA interference for chLEPR reduced the induction rate of luciferase activity by leptin in CHO-chLEPR cells. Furthermore, we found that leptin phosphorylated STAT3 and increased luciferase activity in LMH cells, a chicken hepatoma cell line, transiently expressing chLEPR. These results strongly suggest that the chLEPR is functional in activating the JAK-STAT pathway, which may indicate that the LEPR expressed in chicken tissues is capable of binding endogenous ligand as well as exogenous mammalian leptin, leading to physiological actions.

Induction of food intake by a noradrenergic system using clonidine and fusaric acid in the neonatal chick

To clarify noradrenergic systems on food intake of the neonatal chicks, we examined the effects of i.c.v injection of clonidine (CLON), an alpha2-receptor agonist, and fusaric (5-butylpicolinic) acid (FA), a dopamine (DA)-beta-hydroxylase (DBH) inhibitor. Although a high dose (250 ng) of CLON induced a narcoleptic response and reduced food intake, food intake at 30 min post-injection was enhanced by lower doses (25 and 50 ng) of CLON. Central administration of FA (25, 50 and 100 microg) increased food intake in a dose-dependent fashion. It is suggested that feeding behavior is stimulated by low levels of CLON and decreased by further production of norepinephrine (NE), and FA may play the disturbance of sleeping and then enhance food intake.

Feeding responses to several neuropeptide Y receptor agonists in the neonatal chick

Neuropeptide Y is one of the most potent neuropeptides known to induce feeding in animals, and has been suggested to be a physiological signal for food intake. It has been also reported that intracerebroventricular injection of neuropeptide Y stimulates feeding behavior of the neonatal chick. There are many neuropeptide Y receptor agonists that have not been investigated in feeding response of the neonatal chick. The aim of this study is to elucidate whether central injection of several neuropeptide Y receptor agonists stimulates feeding of the neonatal chick over 2 h. We found that central injections of [Leu(31), Pro(34)]neuropeptide Y, peptide YY, human pancreatic polypeptide and rat pancreatic polypeptide significantly stimulated food intake of neonatal chicks throughout the 2-h post-injection period. Neuropeptide Y-(13-36) significantly stimulated feeding at 30 min, but not thereafter. [D-Trp(32)]neuropeptide Y stimulated feeding at 60 and 120 min, but not 30 min, post-injection. Central administration of rat pancreatic polypeptide, which does not increase food intake in rats, stimulated feeding in chicks. This result reflects structural differences of the neuropeptide Y receptor subtypes and/or differences in mechanisms stimulating feeding behavior between mammals and chickens. In conclusion, neuropeptide Y receptor agonists, except for neuropeptide Y-(13-36), are potent stimulators of food intake in the neonatal chick.

Intracerebroventricular injection of mammalian motilin, melanin-concentrating hormone or galanin does not stimulate food intake in neonatal chicks.

1. Several neural peptides are known to stimulate feeding behaviour in mammalian species. The aim of this study was to elucidate whether central injection of mammalian motilin, melanin-concentrating hormone (MCH) or galanin stimulates feeding in the neonatal chick. 2. None of the peptides applied here enhanced the food intake of the chick. 3. It is suggested that motilin, MCH and galanin, at least those of mammalian origin, may not regulate feeding in neonatal chicks, when administered to the central nervous system.

Effects of various μ- and δ-opioid ligands on food intake in the meat-type chick

Abstract The present study was designed to examine the effects of μ- and δ-opioid receptor ligands on feeding behavior in meat-type chicks. Intracerebroventricular (ICV) injection of naltrexone (μ- and δ-antagonist), β-funaltrexamine (β-FNA; μ-antagonist), ICI-174,864 (ICI; δ-antagonist), or naloxonazine (NAL; μ1-antagonist) significantly decreased deprivation-induced feeding at 30 min postinjection. Co-injection of β-FNA, but not NAL, significantly blocked the depressive effect of [ d -Ala2, N-MePhe4, Gly5-ol]-enkephalin (μ-opioid agonist) under ad libitum conditions. Central injection of ICI attenuated significant effects of [ d -Pen2,5]-enkephalin (δ-opioid agonist) on feeding behavior in ad libitum fed chicks. Co-injection of β-FNA, but not ICI, significantly attenuated the orexigenic effect of [ d -Ala2, d -Leu3]-enkephalin (μ- and δ-opioid agonist). These results suggest that the endogenous opioid peptides, which act on the μ- and/or δ-opioid receptor, have an important role in feeding behavior in the central nervous system of meat-type chicks.

Brain-derived mast cells could mediate histamine-induced inhibition of food intake in neonatal chicks

In the present study, the effect of intracerebroventricular (i.c.v.) administration of histamine on food intake of neonatal chicks was examined over 2 h. Histamine (100, 200 or 400 nmol, respectively) was injected in the lateral ventricle of 2-day-old chicks, and cumulative food intakes were measured. i.c.v. injection of histamine significantly inhibited food intake in a dose-dependent manner. In addition, compound 48/80, which causes degranulation of mast cells and release of histamine, or thioperamide, which is an antagonist of the histamine H3 autoreceptor and increases histamine release from histaminergic nerve terminals, was injected i.c.v. to clarify whether mast cell- or neuron-derived histamine in the central nervous system of chicks is essential to the feeding inhibition. Central administration of compound 48/80 inhibited food intake with a dose-dependent manner, but thioperamide had no effect on feeding. An inhibitor of mast cell degranulation, sodium cromoglycate, somewhat attenuated food intake inhibited by compound 48/80. These results suggest that brain-derived mast cells could be a major source of histamine in the inhibition of food intake of neonatal chicks.