The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Sandra L. Rodriguez-zas - One of the best experts on this subject based on the ideXlab platform.
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Genome-wide census and expression profiling of chicken <B>NeuropeptideB> and prohormone convertase genes
Neuropeptides, 2009Co-Authors: Kristin Delfino, Jonathan V. Sweedler, Bruce R. Southey, Sandra L. Rodriguez-zasAbstract:<B>NeuropeptideB>s regulate cell-cell signaling and influence many Biological processes in verteBrates, including development, growth, and reproduction. The complex processing of <B>NeuropeptideB>s from prohormone proteins By prohormone convertases, comBined with the evolutionary distance Between the chicken and mammalian species that have experienced extensive <B>NeuropeptideB> research, has led to the empirical confirmation of only 18 chicken prohormone proteins. To expand our knowledge of the <B>NeuropeptideB> and prohormone convertase gene complement, we performed an exhaustive survey of the chicken genomic, EST, and proteomic dataBases using a list of 95 <B>NeuropeptideB> 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 <B>NeuropeptideB> genes (apelin, cocaine-and amphetamine-regulated transcript protein, insulin-like 5, <B>NeuropeptideB> S, and <B>NeuropeptideB> B) previously unknown in chicken were identified and 62 genes were confirmed. Although most <B>NeuropeptideB> gene families known in human are present in chicken, there are several gene not present in the chicken. Conversely, several chicken <B>NeuropeptideB> 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 <B>NeuropeptideB>s is similar Between species. <B>NeuropeptideB> 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
Takeshi Sakurai - One of the best experts on this subject based on the ideXlab platform.
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MesolimBic <B>NeuropeptideB> W coordinates stress responses under novel environments
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Toshiyuki Motoike, Takeshi Sakurai, S. Clay Williams, Christopher M. Sinton, Robert E Hammer, Hirokazu Tanaka, Jeffrey M. Long, Amber Skach, Masashi YanagisawaAbstract:<B>NeuropeptideB> B (NPB) and <B>NeuropeptideB> W (NPW) are endogenous <B>NeuropeptideB> ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimBic region possess tyrosine hydroxylase immunoreactivity, indicating that a small suBset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limBic system nuclei in adult mouse Brain: the lateral Bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhiBition of cellular activity, But this stress-induced inhiBition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was aBnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the Behavior of NPW(-/-) mice in a haBituated environment was indistinguishaBle from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.
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NPBWR1 and NPBWR2: Implications in Energy Homeostasis, Pain, and Emotion
Frontiers in endocrinology, 2013Co-Authors: Takeshi SakuraiAbstract:<B>NeuropeptideB> B/W receptor 1 (NPBWR1) and NPBWR2 had Been known as orphan receptors GPR7 and 8, respectively. Endogenous peptide ligands of these receptors, <B>NeuropeptideB> B and <B>NeuropeptideB> W, were identified in 2002 and 2003 (1-3). These peptides have Been implicated in regulation of feeding Behavior, energy homeostasis, neuroendocrine function, and modulating inflammatory pain. In addition, strong and discrete expression of their receptors in the extended amygdala and Bed nucleus of the stria terminalis suggests a potential role in regulating stress responses, emotion, anxiety and fear. Recent studies of NPB/NPW using Both pharmacological and phenotypic analyses of genetically engineered mice as well as a human study support this hypothesis.
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A single nucleotide polymorphism of the <B>NeuropeptideB> B/W receptor-1 gene influences the evaluation of facial expressions.
PloS one, 2012Co-Authors: Noriya Watanabe, Naoki Furutani, Natsuko Tsujino, Takeshi Sakurai, Mari Wada, Yoko Irukayama-tomobe, Yousuke Ogata, Mika Suzuki, Miyuki YamamotoAbstract:<B>NeuropeptideB> B/W receptor-1 (NPBWR1) is expressed in discrete Brain regions in rodents and humans, with particularly strong expression in the limBic system, including the central nucleus of the amygdala. Recently, Nagata-Kuroiwa et al. reported that NpBwr1−/− mice showed changes in social Behavior, suggesting that NPBWR1 plays important roles in the emotional responses of social interactions. The human NPBWR1 gene has a single nucleotide polymorphism at nucleotide 404 (404A>T; SNP rs33977775). This polymorphism results in an amino acid change, Y135F. The results of an in vitro experiment demonstrated that this change alters receptor function. We investigated the effect of this variation on emotional responses to stimuli of showing human faces with four categories of emotional expressions (anger, fear, happiness, and neutral). SuBjects' emotional levels on seeing these faces were rated on scales of hedonic valence, emotional arousal, and dominance (V-A-D). A significant genotype difference was oBserved in valence evaluation; the 404AT group perceived facial expressions more pleasantly than did the 404AA group, regardless of the category of facial expression. Statistical analysis of each comBination of [V-A-D and facial expression] also showed that the 404AT group tended to feel less suBmissive to an angry face than did the 404AA group. Thus, a single nucleotide polymorphism of NPBWR1 seems to affect human Behavior in a social context.
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Circadian characteristics of mice depleted with GPR7.
Biomedical research (Tokyo Japan), 2009Co-Authors: Naohiro Uchio, Mari Hondo, Takeshi Sakurai, Masao Doi, Masahiro Matsuo, Fumiyoshi Yamazaki, Yasutaka Mizoro, Hitoshi OkamuraAbstract:GPR7, now known as a receptor of <B>NeuropeptideB> B and <B>NeuropeptideB> W, is expressed in neurons of the suprachiasmatic nucleus (SCN), the mammalian circadian center. By the quantitative in situ hyBridization, we demonstrated that GPR7 mRNA showed a significant circadian rhythm in the SCN showing a peak at early suBjective night in Both light-dark and constant dark. We characterized the circadian feature of GPR7-knockout mice, But the period length and the phase-dependent phase shift to light exposure were not disordered in GPR7-knockout mice. Moreover, the food-anticipatory Behavior in restricted feeding schedule was oBserved in this gene-deleted mouse similar to wild-type. These results indicate that the role of GPR7 may Be suBtle or limited in relation to the circadian clock despite its roBust expression in the SCN.
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Effect of <B>NeuropeptideB> B on feeding Behavior is influenced By endogenous corticotropin-releasing factor activities.
Regulatory peptides, 2008Co-Authors: Shizu Aikawa, Makoto Ishii, Masashi Yanagisawa, Yuzuru Sakakibara, Takeshi SakuraiAbstract:Decrease in food intake is commonly seen in the mammalian response to stress. Corticotropin-releasing factor (CRF) is a factor that modulates feeding Behavior under these stressful conditions. We previously reported that <B>NeuropeptideB> B (NPB) exerts strong synergistic anorectic effects in mice when co-administered with CRF. Tissue distriButions of <B>NeuropeptideB> B/W receptor-1 (NPBWR1) and NPB suggest that this <B>NeuropeptideB> system also plays a role in regulating emotion and stress responses. In this study, we examined whether the effects of NPB are altered By endogenous CRFergic tone. During the light period, NPB alone did not show any effect on feeding Behavior when administered intracereBroventricularly in mice; however, NPB increased food intake when co-administered with astressin, a potent non-selective CRF receptor antagonist. On the other hand, during the dark period, administration of NPB resulted in a strong inhiBition of feeding Behavior. The effects were almost completely aBolished when astressin was co-administered. Finally, after surgical stress, a semi-chronic stressor, NPB exerted potent anorectic effects on mice. In striking contrast, co-administration of astressin and NPB increased food intake under surgical stress conditions. These data suggest that the effects of NPB are greatly influenced By the endogenous CRFergic tone.
Ludwik K Malendowicz - One of the best experts on this subject based on the ideXlab platform.
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<B>NeuropeptideB> B and W regulate leptin and resistin secretion, and stimulate lipolysis in isolated rat adipocytes.
Regulatory peptides, 2012Co-Authors: Marek Skrzypski, Tatiana Wojciechowicz, Dawid Szczepankiewicz, Mathias Z. Strowski, Ewa Pruszyńska-oszmałek, Marcin Ruciński, Maciej Sassek, Przemysław Kaczmarek, Paweł A Kołodziejski, Ludwik K MalendowiczAbstract:<B>NeuropeptideB> B (NPB) and W (NPW) regulate food intake and energy homeostasis in humans via two G-protein-coupled receptor suBtypes, termed as GPR7 and GPR8. Rodents express GPR7 only. In animals, NPW decreases insulin and leptin levels, whereas the deletion of either NPB or GPR7 leads to oBesity and hyperphagia. MetaBolic and endocrine in vitro activities of NPW/NPB in adipocytes are unknown. We therefore characterize the effects of NPB and NPW on the secretion and expression of leptin and resistin, and on lipolysis, using rat adipocytes. Isolated rat adipocytes express GPR7 mRNA. NPB and NPW are expressed in macrophages and preadipocytes But are aBsent in mature adipocytes. Both, NPB and NPW reduce the secretion and expression of leptin from isolated rat adipocytes. NPB stimulates the secretion and expression of resistin, whereas Both, NPB and NPW increase lipolysis. Our study demonstrates for the first time that NPB and NPW regulate the expression and secretion of leptin and resistin, and increase lipolysis in isolated rat adipocytes. These effects are presumaBly mediated via GPR7. The increase of resistin secretion, stimulation of lipolysis and the decrease of leptin secretion may represent mechanisms, through which NPB and NPW can affect glucose and lipid homeostasis, and food intake in rodents.
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<B>NeuropeptideB> B (NPB) and <B>NeuropeptideB> W (NPW) system in cultured rat calvarial osteoBlast-like (ROB) cells: NPW and NPB inhiBit proliferative activity of ROB cells.
International journal of molecular medicine, 2009Co-Authors: Agnieszka Ziolkowska, Marcin Ruciński, Marianna Tyczewska, Ludwik K MalendowiczAbstract:<B>NeuropeptideB>s B (NPB) and W (NPW) have Been identified as endogenous ligands of two G-protein-coupled receptors, <B>NeuropeptideB>s B/W receptor 1 (NPBWR1, formerly known as GPR7) and <B>NeuropeptideB>s B/W receptor 2 (NPBWR2, formerly known as GPR8). In rodents where NPBWR2 is aBsent, its counterpart is named the similar to <B>NeuropeptideB>s B/W receptor 2 (similar to NPBWR2, formerly GPR8-like). Both NPB and NPW play a role in the control of feeding, neuroendocrine axis functions, memory and learning processes as well as in pain regulation. The present study aimed to investigate the expression of NPB, NPW, NPBWR1 and the similar to NPBWR2 genes in cultured rat calvarial osteoBlast-like (ROB) cells and the effects of Both peptides on proliferative activity and osteocalcin secretion By ROB cells. Classic RT-PCR technique revealed the presence of ppNPB mRNA, ppNPW mRNA, and NPBWR1 mRNA, But not similar to NPBWR2 mRNA in ROB cells. QPCR revealed gradual (days 7, 14 and 21 of culture) increase of the ppNPB gene expression, while expression of ppNPW gene was the highest at day 14 and was comparaBle to that seen in freshly isolated cells. In ROB cells, expression of NPBWR1 gene was notaBle at day 7 of culture, lower at day 21, and negligiBle at day 14. Neither NPB nor NPW changed osteocalcin secretion By cultured osteoBlast-like cells while Both <B>NeuropeptideB>s inhiBited their proliferative activity. Results of the present study suggest that the systems of NPW, NPB and NPBWR1 directly regulate proliferative activity of cultured rat calvaria osteoBlast-like cells. The physiological significance of this osteoBlastic system remains unclear, and requires further investigation.
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<B>NeuropeptideB> W exerts a potent suppressive effect on Blood leptin and insulin concentrations in the rat
International journal of molecular medicine, 2007Co-Authors: Marcin Ruciński, Krzysztof W. Nowak, Joanna Chmielewska, Agnieszka Ziolkowska, Ludwik K MalendowiczAbstract:<B>NeuropeptideB> B/W receptor 1 (NPBWR1) and <B>NeuropeptideB> B/W receptor 2 (NPBWR2) are two structurally related orphan receptors linked to protein G. In rodents NPBWR2 is aBsent, and its counterpart is descriBed as Being similar to <B>NeuropeptideB> B/W receptor 2. Endogenous ligands of these receptors have Been identified. One of them is 29 amino acid residues long, uniquely modified with Bromine and, thus, termed <B>NeuropeptideB> B (NPB). The other, <B>NeuropeptideB> W (NPW), has Been identified in two molecular forms of 23 and 30 amino acids (NPW23 and NPW30), respectively. Both NPB and NPW affect food intake and energy expenditure. Since leptin, a potent anti-oBesity hormone, and insulin are involved in the control of energy homeostasis, the present study aimed to investigate whether NPB and NPW affect leptin and insulin secretion in the rat. RT-PCR technique revealed the presence of ppNPB, ppNPW, NPBWR1 and NPBWR2-like mRNAs in isolated pancreatic islets of the rat. NPB and NPW immunoreactivities were oBserved in all of the cells of the pancreatic islets. Only when a higher dose was administered (3 nmol/100 g Body weight) did NPW transiently lower Blood insulin levels whereas NPB injection did not alter insulinaemia in the studied rats. At 30 min, But not 60, of the experiment, NPW notaBly lowered Blood leptin concentrations at Both tested doses. On the contrary, NPB injections had no effect on Blood leptin and insulin concentrations. Thus, the results suggest that NPW But not NPB exerts a potent suppressive effect on Blood leptin concentrations in the rat, and this mechanism may Be involved in NPW regulation of energy homeostasis.
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Effects of <B>NeuropeptideB>s B and W on the secretion and growth of rat adrenocortical cells
International journal of molecular medicine, 2004Co-Authors: Anna Hochol, Marcin Ruciński, Agnieszka Ziolkowska, Giovanna Albertin, Gastone G. Nussdorfer, Raffaella Spinazzi, Ludwik K MalendowiczAbstract:<B>NeuropeptideB>-B (NPB) and <B>NeuropeptideB>-W (NPW) are recently discovered endogenous ligands of the GPR7- and GPR8-receptors (R), which in humans are expressed in the hypothalamus and proBaBly involved in the regulation of energy homeostasis and neuroendocrine axes. GPR8-Rs are aBsent in rodents, where the GPR8-like-R has Been descriBed. Reverse transcription-polymerase chain reaction detected the expression of NPB, NPW, GPR7-R and GPR8-like-R mRNAs in rat adrenocortical cells (Both freshly-dispersed and 4-day-cultured cells). NPB did not acutely (60-min exposure) alter Basal aldosterone secretion from freshly dispersed zona glomerulosa cells, while NPW raised it. Both NPB and NPW enhanced ACTH-stimulated aldosterone secretion and did not affect either Basal or ACTH-stimulated corticosterone production By dispersed zona fasciculata/reticularis (ZF/R) cells. The prolonged (4-day) exposure to NPW, But not NPB, raised corticosterone secretion from cultured ZF/R cells, and Both <B>NeuropeptideB>s increased the proliferation rate of cultured cells. Taken together, our findings indicate that NPB and NPW affect rat adrenocortical function, so they may Be included in that large family of peptides involved in the autocrine-paracrine stimulation of secretion and growth of adrenal cortex.
Masashi Yanagisawa - One of the best experts on this subject based on the ideXlab platform.
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MesolimBic <B>NeuropeptideB> W coordinates stress responses under novel environments
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Toshiyuki Motoike, Takeshi Sakurai, S. Clay Williams, Christopher M. Sinton, Robert E Hammer, Hirokazu Tanaka, Jeffrey M. Long, Amber Skach, Masashi YanagisawaAbstract:<B>NeuropeptideB> B (NPB) and <B>NeuropeptideB> W (NPW) are endogenous <B>NeuropeptideB> ligands for the G protein-coupled receptors NPBWR1 and NPBWR2. Here we report that the majority of NPW neurons in the mesolimBic region possess tyrosine hydroxylase immunoreactivity, indicating that a small suBset of dopaminergic neurons coexpress NPW. These NPW-containing neurons densely and exclusively innervate two limBic system nuclei in adult mouse Brain: the lateral Bed nucleus of the stria terminalis and the lateral part of the central amygdala nucleus (CeAL). In the CeAL of wild-type mice, restraint stress resulted in an inhiBition of cellular activity, But this stress-induced inhiBition was attenuated in the CeAL neurons of NPW(-/-) mice. Moreover, the response of NPW(-/-) mice to either formalin-induced pain stimuli or a live rat (i.e., a potential predator) was aBnormal only when they were placed in a novel environment: The mice failed to show the normal species-specific self-protective and aversive reactions. In contrast, the Behavior of NPW(-/-) mice in a haBituated environment was indistinguishaBle from that of wild-type mice. These results indicate that the NPW/NPBWR1 system could play a critical role in the gating of stressful stimuli during exposure to novel environments.
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Transient expression of <B>NeuropeptideB> W in postnatal mouse hypothalamus--a putative regulator of energy homeostasis.
Neuroscience, 2015Co-Authors: T. Motoike, Christopher M. Sinton, Amber Skach, J. K. Godwin, Maya Yamazaki, Manabu Abe, Rie Natsume, Kenji Sakimura, Masashi YanagisawaAbstract:<B>NeuropeptideB> B and W (NPB and NPW) are cognate peptide ligands for NPBWR1 (GPR7), a G protein-coupled receptor. In rodents, they have Been implicated in the regulation of energy homeostasis, neuroendocrine/autonomic responses, and social interactions. Although localization of these peptides and their receptors in adult rodent Brain has Been well documented, their expression in mouse Brain during development is unknown. Here we demonstrate the transient expression of NPW mRNA in the dorsomedial hypothalamus (DMH) of postnatal mouse Brain and its co-localization with <B>NeuropeptideB> Y (NPY) mRNA. Neurons expressing Both NPW and NPY mRNAs Begin to emerge in the DMH at aBout postnatal day 0 (P-0) through P-3. Their expression is highest around P-14, declines after P-21, and By P-28 only a faint expression of NPW and NPY mRNA remains. In P-18 Brains, we detected NPW neurons in the region spanning the suBincertal nucleus (SuBI), the lateral hypothalamic (LH) perifornical (PF) areas, and the DMH, where the highest expression of NPW mRNA was oBserved. The majority of these postnatal hypothalamic NPW neurons co-express NPY mRNA. A cross of NPW-iCre knock-in mice with a Cre-dependent tdTomato reporter line revealed that more than half of the reporter-positive neurons in the adult DMH, which mature from the transiently NPW-expressing neurons, are sensitive to peripherally administrated leptin. These data suggest that the DMH neurons that transiently co-express NPW and NPY in the peri-weaning period might play a role in regulating energy homeostasis during postnatal development.
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Effect of <B>NeuropeptideB> B on feeding Behavior is influenced By endogenous corticotropin-releasing factor activities.
Regulatory peptides, 2008Co-Authors: Shizu Aikawa, Makoto Ishii, Masashi Yanagisawa, Yuzuru Sakakibara, Takeshi SakuraiAbstract:Decrease in food intake is commonly seen in the mammalian response to stress. Corticotropin-releasing factor (CRF) is a factor that modulates feeding Behavior under these stressful conditions. We previously reported that <B>NeuropeptideB> B (NPB) exerts strong synergistic anorectic effects in mice when co-administered with CRF. Tissue distriButions of <B>NeuropeptideB> B/W receptor-1 (NPBWR1) and NPB suggest that this <B>NeuropeptideB> system also plays a role in regulating emotion and stress responses. In this study, we examined whether the effects of NPB are altered By endogenous CRFergic tone. During the light period, NPB alone did not show any effect on feeding Behavior when administered intracereBroventricularly in mice; however, NPB increased food intake when co-administered with astressin, a potent non-selective CRF receptor antagonist. On the other hand, during the dark period, administration of NPB resulted in a strong inhiBition of feeding Behavior. The effects were almost completely aBolished when astressin was co-administered. Finally, after surgical stress, a semi-chronic stressor, NPB exerted potent anorectic effects on mice. In striking contrast, co-administration of astressin and NPB increased food intake under surgical stress conditions. These data suggest that the effects of NPB are greatly influenced By the endogenous CRFergic tone.
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<B>NeuropeptideB> B-deficient mice demonstrate hyperalgesia in response to inflammatory pain
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Michele A. Kelly, Toshiyuki Motoike, Carsten T. Beuckmann, S. Clay Williams, Christopher M. Sinton, James A. Richardson, Robert E Hammer, Mary G. Garry, Masashi YanagisawaAbstract:<B>NeuropeptideB> B (NPB) and <B>NeuropeptideB> W (NPW) have Been recently identified as ligands for the G protein-coupled receptor (GPR) 7 and GPR8. The precise in vivo role of this <B>NeuropeptideB>-receptor pathway has not Been fully demonstrated. In this paper, we report that NPB-deficient mice manifest a mild adult-onset oBesity, similar to that reported in GPR7-null mice. NPB-deficient mice also exhiBit hyperalgesia in response to inflammatory pain. Hyperalgesia was not oBserved in response to chemical pain, thermal pain, or electrical stimulation. NPB-deficient mice demonstrated intact Behavioral responses to pain, and learning from the negative reinforcement of electrical stimulation was unaltered. Baseline anxiety was also unchanged as measured in Both the elevated plus maze and time spent immoBile in a novel environment. These data support the idea that NPB is a factor in the modulation of responses to inflammatory pain and Body weight homeostasis.
Kristin Delfino - One of the best experts on this subject based on the ideXlab platform.
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Genome-wide census and expression profiling of chicken <B>NeuropeptideB> and prohormone convertase genes
Neuropeptides, 2009Co-Authors: Kristin Delfino, Jonathan V. Sweedler, Bruce R. Southey, Sandra L. Rodriguez-zasAbstract:<B>NeuropeptideB>s regulate cell-cell signaling and influence many Biological processes in verteBrates, including development, growth, and reproduction. The complex processing of <B>NeuropeptideB>s from prohormone proteins By prohormone convertases, comBined with the evolutionary distance Between the chicken and mammalian species that have experienced extensive <B>NeuropeptideB> research, has led to the empirical confirmation of only 18 chicken prohormone proteins. To expand our knowledge of the <B>NeuropeptideB> and prohormone convertase gene complement, we performed an exhaustive survey of the chicken genomic, EST, and proteomic dataBases using a list of 95 <B>NeuropeptideB> 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 <B>NeuropeptideB> genes (apelin, cocaine-and amphetamine-regulated transcript protein, insulin-like 5, <B>NeuropeptideB> S, and <B>NeuropeptideB> B) previously unknown in chicken were identified and 62 genes were confirmed. Although most <B>NeuropeptideB> gene families known in human are present in chicken, there are several gene not present in the chicken. Conversely, several chicken <B>NeuropeptideB> 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 <B>NeuropeptideB>s is similar Between species. <B>NeuropeptideB> 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