Neuropeptides

Editorial Board

2010-02-01

The regulatory role of neurotensin on the hypothalamic–anterior pituitary axons: Emphasis on the control of thyroid-related functions

2009-10-30

Abstract: Neurotensin (NT) is a 13 amino acid neurohormone and/or neuromodulator, located in the synaptic vesicles and released from the neuronal terminals in a calcium-dependent manner. This peptide is present among mammalian and nonmammalian species, mainly in the central nervous system and the gastrointestinal tract. Due to its neuroendocrine activity, NT has been related to the pathophysiology of a series of disorders, such as schizophrenia, drug-abuse, Parkinson’s disease, cancer, stroke, eating disorders and other neurodegenerative conditions. Moreover, NT participates in the physiology of pain-induction, central blood pressure control and inflammation. NT also plays an important interactive role in all components of the hypothalamic–anterior pituitary circuit, which is mediated by an endocrine, paracrine or/and autocrine manner, towards most of the anatomical regions that define this circuit. A considerable amount of data implicates NT in thyroid-related regulation through this circuit, the exact mechanisms of which should be further investigated for the potential development of more targeted approaches towards the treatment of thyroid-related endocrine diseases. The aim of this study was to provide an up-to-date review of the literature concerning the regulatory role of NT on the hypothalamic–anterior pituitary axons, with an emphasis on the control of thyroid-related functions.

Ethanol exposure selectively alters β-endorphin content but not [3H]-DAMGO binding in discrete regions of the rat brain

M. Leriche, M. Méndez — 2009-12-23

Abstract: The dopaminergic mesocorticolimbic system plays an important role in the reinforcing effects of ethanol. Opioid peptides modulate the activity of this system and have been suggested to mediate, at least in part, the reinforcing properties of ethanol. Thus, beta-endorphin (β-END) could participate in the development of ethanol reinforcement and addiction. The aim of this work was to investigate the acute and chronic ethanol effects on β-END content in regions of the mesolimbic system and to examine if chronic ethanol treatment alters ligand binding to mu opioid receptor (μOR). Male Wistar rats received a single acute ethanol dose of 2.5g/kg or water by intra-gastric administration. For chronic ethanol treatment experiments, one group of rats was given ethanol (10% v/v solution) to drink, two groups were given equivalent volumes of sucrose (14.14% isocaloric solution) or water, respectively, and a fourth group had ad libitum access to food and water. Treatment was followed for 4weeks. Beta-endorphin content in brain regions was quantified by radioimmunoassay and ligand binding studies to μOR were performed by quantitative autoradiography using 8nM [3H]-DAMGO as radioligand. Acute ethanol decreased β-END content in the hypothalamus (26%) 1h after administration. No ethanol effects were observed in the midbrain, ventral tegmental area, substantia nigra, nucleus accumbens, nucleus accumbens-septum and prefrontal cortex. Chronic ethanol treatment neither changed β-END levels nor [3H]-DAMGO binding to mu opioid receptors in any of the regions studied. However, β-END levels in the sucrose group were significantly increased in the nucleus accumbens and substantia nigra, in comparison to all other groups. These findings suggest that different neural mechanisms and specific brain regions may be involved in the reinforcing effects of ethanol and sucrose.

Differential effect of prolonged food restriction and fasting on hypothalamic malonyl-CoA concentration and expression of orexigenic and anorexigenic neuropeptides genes in rats

2009-12-14

Abstract: Several lines of evidence suggest that malonyl-CoA in the hypothalamus plays an important role in monitoring and modulating body energy balance. In fasted state the level of malonyl-CoA concentration significantly decreases. Simultaneously, orexigenic neuropeptides (NPY – neuropeptide Y, AgRP – agouti-related peptide) genes are expressed at high level, whereas anorexigenic neuropeptides (CART – cocaine-and amphetamine-regulated transcript, POMC – proopiomelanocortin) genes are expressed at low level. When food intake resumes, opposite effect is observed. This study examined the effect of prolonged food restriction, common in humans trying to lose body weight on expression of orexigenic and anorexigenic neuropetides genes and on malonyl-CoA content in rat whole hypothalamus.We observed an increase of NPY and AgRP mRNA levels in hypothalamus of rats kept on 30days-long food restriction (50% of the amount of food consumed by controls). Simultaneously, a decrease of CART and POMC mRNA levels occurred. Refeeding caused a decrease in NPY and POMC mRNA levels without effect on AgRP and CART mRNA. Surprisingly, both prolonged food restriction and food restriction/refeeding caused the increase of malonyl-CoA level in whole hypothalamus. In contrast, fasting for 24h caused the decrease of malonyl-CoA level, which was associated with the up-regulation of NPY and AgRP genes expression and down-regulation of CART and POMC genes expression. After refeeding opposite effect was observed.These results indicate that prolonged food restriction and acute fasting, conditions in which energy expenditure exceeds intake, differentially affect malonyl-CoA concentration and similarly affect orexigenic and anorexigenic neuropeptide genes expression in whole rat hypothalamus.

Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages

Tihomir Balog, Ana Šarić, Sandra Sobočanec, Borka Kušić, Tatjana Marotti — 2009-12-10

Abstract: Endomorphins are newly discovered μ-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30min pretreatment with μ-receptor selective antagonist β-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

Genome-wide census and expression profiling of chicken neuropeptide and prohormone convertase genes

K.R. Delfino, B.R. Southey, J.V. Sweedler, S.L. Rodriguez-Zas — 2009-12-14

Abstract: Neuropeptides regulate cell-cell signaling and influence many biological processes in vertebrates, including development, growth, and reproduction. The complex processing of neuropeptides from prohormone proteins by prohormone convertases, combined with the evolutionary distance between the chicken and mammalian species that have experienced extensive neuropeptide research, has led to the empirical confirmation of only 18 chicken prohormone proteins. To expand our knowledge of the neuropeptide and prohormone convertase gene complement, we performed an exhaustive survey of the chicken genomic, EST, and proteomic databases using a list of 95 neuropeptide and 7 prohormone convertase genes known in other species. Analysis of the EST resources and 22 microarray studies offered a comprehensive portrait of gene expression across multiple conditions. Five neuropeptide genes (apelin, cocaine-and amphetamine-regulated transcript protein, insulin-like 5, neuropeptide S, and neuropeptide B) previously unknown in chicken were identified and 62 genes were confirmed. Although most neuropeptide gene families known in human are present in chicken, there are several gene not present in the chicken. Conversely, several chicken neuropeptide genes are absent from mammalian species, including C-RF amide, c-type natriuretic peptide 1 precursor, and renal natriuretic peptide. The prohormone convertases, with one exception, were found in the chicken genome. Bioinformatic models used to predict prohormone cleavages confirm that the processing of prohormone proteins into neuropeptides is similar between species. Neuropeptide genes are most frequently expressed in the brain and head, followed by the ovary and small intestine. Microarray analyses revealed that the expression of adrenomedullin, chromogranin-A, augurin, neuromedin-U, platelet-derived growth factor A and D, proenkephalin, relaxin-3, prepronociceptin, and insulin-like growth factor I was most susceptible (P-value<0.005) to changes in developmental stage, gender, and genetic line among other conditions studied. Our complete survey and characterization facilitates understanding of neuropeptides genes in the chicken, an animal of importance to biomedical and agricultural research.

PACAP and VIP affect NF1 expression in rat malignant peripheral nerve sheath tumor (MPNST) cells

2009-11-18

Abstract: In our previous study we have identified PACAP, VIP and their receptors in rat malignant peripheral nerve sheath tumor (MPNST) cells, thus showing anti-apoptotic roles. Recently it has been shown that the tumor suppressor neurofibromin, encoded by the Neurofibromatosis type I (NF1) gene, promotes MPNST cells sensitivity to apoptosis after serum withdrawal.In the present study we investigated whether PACAP or VIP negatively regulate NF1 expression under normal or serum-dependent pro-apoptotic culture conditions. Results indicated that serum itself significantly influenced gene and protein levels. In fact, the low NF1 levels of cells cultured in normal serum-containing medium were remarkably increased in cells switched to low- or no-serum after 24h and 48h. Treatment with 100nM PACAP or VIP did not affect NF1 expression when using normal amounts of serum, whereas it significantly inhibited transcript and protein levels both in low- or no-serum cultured cells. In particular, PACAP reduced NF1 levels already after 24h in low-serum cultured cells, while VIP showed a similar effect only after serum deprivation. However, both PACAP and VIP downregulated gene and protein levels within 48h either in low-dose and serum-starved cells. Results were confirmed by fluorescence microscopy, showing that 100nM PACAP or VIP attenuated neurofibromin cytoplasmic localization only in low- or no-serum cultured cells.The present study provides a comprehensive analysis of both neuropeptides effect on NF1 expression in normal, low- or serum-starved MPNST cells, ameliorating the hypothesis that resistance to apoptosis in serum-deprived cells might be correlated to PACAP-/VIP-induced NF1 inhibition.

Effect of serotonergic system on AVP secretion induced by physical exercise

2009-11-16

Abstract: The present study was undertaken in order to establish the possible involvement of serotonergic receptors in the control of physical exercise-stimulated vasopressin secretion. Twenty-one healthy men (divided in three groups of seven) underwent bicycle-ergometer tests until exhaustion: exercise control test (n=21), exercise plus ondansetron, selective 5-HT3 antagonist (n=7), exercise plus buspirone, selective 5-HT1A receptor agonist (n=7), exercise plus sumatriptan, selective 5-HT1D receptor agonist (n=7). AVP levels, physiological and biochemical variables were measured and compared during tests. Results showed that exercise-induced AVP rise did not change after the administration of buspirone and sumatriptan. In contrast, the administration of ondansetron significantly reduced physical exercise-induced AVP rise. Mean peak levels during physical exercise were 4.9 times higher than basal values in the control test and 2.6 times higher than basal values in the ondansetron plus exercise test. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to physical exercise. On the other hand, 5-HT1A and 5-HT1D serotonergic receptors do not appear to be involved in the control of AVP secretion during exercise.

Differential effects of substance P or hemokinin-1 on transient receptor potential channels, TRPV1, TRPA1 and TRPM8, in the rat

Rumi Naono-Nakayama, Natsuki Sunakawa, Tetsuya Ikeda, Toshikazu Nishimori — 2009-11-19

Abstract: Two tachykinin peptides, substance P (SP) and hemokinin-1 (HK-1), and three transient receptor potential (TRP) channels, TRPV1, TRPA1 and TRPM8, are similarly localized in the spinal dorsal horn and dorsal root ganglion, suggesting that TRP channels may be related or modulated by these tachykinin peptides. Thus, to clarify whether the responses of TRP channels are modulated by SP or HK-1, the effects of pretreatment with SP or HK-1 on the induction of scratching behavior by TRP channel agonists were examined. Pretreatment with SP or HK-1 enhanced the induction of scratching behavior by resiniferatoxin, a TRPV1 agonist, whereas scratching behavior induced by menthol, a TRPM8 agonist, was suppressed by pretreatment with these peptides. On the other hand, pretreatment with SP, but not HK-1, suppressed the induction of scratching behavior by cinnamaldehyde, a TRPA1 agonist. Taken together, the present results indicate that SP or HK-1 differentially modulated the response of TRPV1, TRPA1 or TRPM8 channel.

Corrigendum to “Role of NGF in spared DRG following partial dorsal rhizotomy in cats” [Neuropeptides 43(5) (2009) 363–369]

2009-12-14

The affiliation for the first author (Xue Zhou) is hereby replaced with the following: Department of Histology and Neurobiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.

Meetings Calendar

2010-02-01