The Experts below are selected from a list of 16137 Experts worldwide ranked by ideXlab platform
Lenka Maletínská - One of the best experts on this subject based on the ideXlab platform.
-
Cellular Signaling and Anti-Apoptotic Effects of Prolactin-Releasing Peptide and Its Analog on SH-SY5Y Cells.
International journal of molecular sciences, 2020Co-Authors: Anna Zmeškalová, Andrea Popelová, Jaroslav Kuneš, Blanka Železná, Aneta Exnerová, Lenka MaletínskáAbstract:Prolactin-Releasing Peptide (PrRP), a natural ligand for the GPR10 receptor, is a neuroPeptide with anorexigenic and antidiabetic properties. Due to its role in the regulation of food intake, PrRP is a potential drug for obesity treatment and associated type 2 diabetes mellitus (T2DM). Recently, the neuroprotective effects of lipidized PrRP analogs have been proven. In this study, we focused on the molecular mechanisms of action of natural PrRP31 and its lipidized analog palm11-PrRP31 in the human neuroblastoma cell line SH-SY5Y to describe their cellular signaling and possible anti-apoptotic properties. PrRP31 significantly upregulated the phosphoinositide-3 kinase-protein kinase B/Akt (PI3K-PKB/Akt) and extracellular signal-regulated kinase/cAMP response element-binding protein (ERK-CREB) signaling pathways that promote metabolic cell survival and growth. In addition, we proved via protein kinase inhibitors that activation of signaling pathways is mediated specifically by PrRP31 and its palmitoylated analog. Furthermore, the potential neuroprotective properties were studied through activation of anti-apoptotic pathways of PrRP31 and palm11-PrRP31 using the SH-SY5Y cell line and rat primary neuronal culture stressed with toxic methylglyoxal (MG). The results indicate increased viability of the cells treated with PrRP and palm11-PrRP31 and a reduced degree of apoptosis induced by MG, suggesting their potential use in the treatment of neurological disorders.
-
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties.
International journal of molecular sciences, 2019Co-Authors: Veronika Pražienková, Andrea Popelová, Jaroslav Kuneš, Lenka MaletínskáAbstract:Prolactin-Releasing Peptide (PrRP) belongs to the large RF-amide neuroPeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10. Special attention is paid to structure-activity relationship studies on PrRP and its analogs as well as to their effect on different physiological functions, mainly their anorexigenic and neuroprotective features and the regulation of the cardiovascular system, pain, and stress. Additionally, the therapeutic potential of this Peptide and its analogs is explored.
-
Metabolomic Study of Obesity and Its Treatment with Palmitoylated Prolactin-Releasing Peptide Analog in Spontaneously Hypertensive and Normotensive Rats
Journal of proteome research, 2019Co-Authors: Martina Čermáková, Jaroslav Kuneš, Lenka Maletínská, Blanka Železná, Barbora Neprašová, Helena Pelantová, Blanka Šedivá, Petra Tomášová, Marek KuzmaAbstract:In this study, the combination of metabolomics and standard biochemical and biometric parameters was used to describe the metabolic effects of diet-induced obesity and its treatment with the novel antiobesity compound palm11-PrRP31 (palmitoylated Prolactin-Releasing Peptide) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The results showed that SHR on a high-fat (HF) diet were normoglycemic with obesity and hypertension, while WKY on the HF diet were normotensive and obese with prediabetes. NMR-based metabolomics revealed mainly several microbial cometabolites altered by the HF diet, particularly in urine. The HF diet induced similar changes in both models. However, two groups of genotype-specific metabolites were defined: metabolites specific to the genotype at baseline (e.g., 1-methylnicotinamide, phenylacetylglycine, taurine, methylamine) and metabolites reacting specifically to the HF diet in individual genotypes (2-oxoglutarate, dimethylamine, N-butyrylglycine, p-c...
-
Lipidized Prolactin-Releasing Peptide Agonist Attenuates Hypothermia-Induced Tau Hyperphosphorylation in Neurons
Journal of Alzheimer's disease : JAD, 2019Co-Authors: Veronika Pražienková, Jaroslav Kuneš, Martina Holubová, Claire Schirmer, Blanka Železná, Marie-christine Galas, Lenka MaletínskáAbstract:Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of extracellular amyloid plaques and intraneuronal neurofibrillary tangles. These tangles mainly consist of hyperphosphorylated tau protein. As it induces tau hyperphosphorylation in vitro and in vivo, hypothermia is a useful tool for screening potential neuroprotective compounds that ameliorate tau pathology. In this study, we examined the effect of Prolactin-Releasing Peptide (PrRP), its lipidized analog palm11-PrRP31 and glucagon-like-Peptide-1 agonist liraglutide, substances with anorexigenic and antidiabetic properties, on tau phosphorylation and on the main kinases and phosphatases involved in AD development. Our study was conducted in a neuroblastoma cell line SH-SY5Y and rat primary neuronal cultures under normothermic and hypothermic conditions. Hypothermia induced a significant increase in tau phosphorylation at the pThr212 and pSer396/pSer404 epitopes. The palmitoylated analogs liraglutide and palm11-PrRP31 attenuated tau hyperphosphorylation, suggesting their potential use in the treatment of neurodegenerative diseases.
-
Lipidized Prolactin-Releasing Peptide improved glucose tolerance in metabolic syndrome: Koletsky and spontaneously hypertensive rat study
Nutrition & Diabetes, 2018Co-Authors: Barbora Mikulášková, Veronika Pražienková, Jaroslav Kuneš, Jana Zemenová, Martina Holubová, Blanka Železná, Lucie Hrubá, Martin Haluzík, Lenka MaletínskáAbstract:Background/Objectives Prolactin-Releasing Peptide (PrRP) has a potential to decrease food intake and ameliorate obesity, but is ineffective after peripheral administration. We have previously shown that our novel lipidized analogs PrRP enhances its stability in the circulation and enables its central effect after peripheral application. The purpose of this study was to explore if sub-chronic administration of novel PrRP analog palmitoylated in position 11 (palm^11-PrRP31) to Koletsky-spontaneously hypertensive obese rats (SHROB) could lower body weight and glucose intolerance as well as other metabolic parameters. Subjects/Methods The SHROB rats ( n = 16) were used for this study and age-matched hypertensive lean SHR littermates ( n = 16) served as controls. Palm^11-PrRP31 was administered intraperitoneally to SHR and SHROB ( n = 8) at a dose of 5 mg/kg once-daily for 3 weeks. During the dosing period food intake and body weight were monitored. At the end of the experiment the oral glucose tolerance test was performed; plasma and tissue samples were collected. Thereafter, arterial blood pressure was measured. Results At the end of the experiment, vehicle-treated SHROB rats showed typical metabolic syndrome parameters, including obesity, glucose intolerance, dyslipidemia, and hypertension. Peripheral treatment with palm^11-PrRP31 progressively decreased the body weight of SHR rats but not SHROB rats, though glucose tolerance was markedly improved in both strains. Moreover, in SHROB palm^11-PrRP31 ameliorated the HOMA index, insulin/glucagon ratio, and increased insulin receptor substrate 1 and 2 expression in fat and insulin signaling in the hypothalamus, while it had no effect on blood pressure. Conclusions We demonstrated that our new lipidized PrRP analog is capable of improving glucose tolerance in obese SHROB rats after peripheral application, suggesting that its effect on glucose metabolism is independent of leptin signaling and body weight lowering. These data suggest that this analog has the potential to be a compound with both anti-obesity and glucose-lowering properties.
Tatsushi Onaka - One of the best experts on this subject based on the ideXlab platform.
-
Involvement of Prolactin‐Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake
Journal of neuroendocrinology, 2013Co-Authors: M. Yamashita, Yuki Takayanagi, Masahide Yoshida, Katsuhiko Nishimori, M. Kusama, Tatsushi OnakaAbstract:Food intake activates neurones expressing Prolactin-Releasing Peptide (PrRP) in the medulla oblongata and oxytocin neurones in the hypothalamus. Both PrRP and oxytocin have been shown to have an anorexic action. In the present study, we investigated whether the activation of oxytocin neurones following food intake is mediated by PrRP. We first examined the expression of PrRP receptors (also known as GPR10) in rats. Immunoreactivity of PrRP receptors was observed in oxytocin neurones and in vasopressin neurones in the paraventricular and supraoptic nuclei of the hypothalamus and in the bed nucleus of the stria terminalis. Application of PrRP to isolated supraoptic nuclei facilitated the release of oxytocin and vasopressin. In mice, re-feeding increased the expression of Fos protein in oxytocin neurones of the hypothalamus and bed nucleus of the stria terminalis. The increased expression of Fos protein in oxytocin neurones following re-feeding or i.p. administration of cholecystokinin octaPeptide (CCK), a peripheral satiety factor, was impaired in PrRP-deficient mice. CCK-induced oxytocin increase in plasma was also impaired in PrRP-deficient mice. Furthermore, oxytocin receptor-deficient mice showed an increased meal size, as reported in PrRP-deficient mice and in CCKA receptor-deficient mice. These findings suggest that PrRP mediates, at least in part, the activation of oxytocin neurones in response to food intake, and that the CCK–PrRP–oxytocin pathway plays an important role in the control of the termination of each meal.
-
Roles of prolactin‐releasing Peptide and RFamide related Peptides in the control of stress and food intake
The FEBS journal, 2010Co-Authors: Yuki Takayanagi, Tatsushi OnakaAbstract:Subsequent to the isolation of the first recognized RFamide neuroPeptide, FMRFamide, from the clam, a large number of these Peptides have been identified. There are now five groups of RFamide Peptides identified in mammals. RFamide Peptides show diversity with respect to their N-terminal sequence and biological activity. RFamide Peptides have been implicated in a variety of roles, including energy metabolism, stress and pain modulation, as well as effects in the neuroendocrine and cardiovascular systems. In the present minireview, we focus on Prolactin-Releasing Peptide (PrRP) and RFamide related Peptide (RFRP) with respect to their roles in the control of energy metabolism and stress responses. Both food intake and stressful stimuli activate PrRP neurons. The administration of PrRP affects energy metabolism and neuroendocrine systems. PrRP-deficient or PrRP receptor-deficient mice show abnormal energy metabolism and/or stress responses. On the other hand, RFRP neurons are activated by stressful stimuli and the administration of RFRP induces neuroendocrine and behavioral stress responses. Taken together, these data suggests that PrRP and RFRP neurons play a role in the control of energy metabolism and/or stress responses.
-
Metabolic and stress-related roles of Prolactin-Releasing Peptide.
Trends in endocrinology and metabolism: TEM, 2010Co-Authors: Tatsushi Onaka, Yuki Takayanagi, Gareth LengAbstract:In the modern world, improvements in human health can be offset by unhealthy lifestyle factors, including the deleterious consequences of stress and obesity. For energy homeostasis, humoral factors and neural afferents from the gastrointestinal tract, in combination with long-term nutritional signals, communicate information to the brain to regulate energy intake and expenditure. Energy homeostasis and stress interact with each other, and stress affects both food intake and energy expenditure. Prolactin-Releasing Peptide, synthesized in discrete neuronal populations in the hypothalamus and brainstem, plays an important role in integrating these responses. This review describes how Prolactin-Releasing Peptide neurons receive information concerning both internal metabolic states and environmental conditions, and play a key role in energy homeostasis and stress responses.
-
Endogenous Prolactin-Releasing Peptide regulates food intake in rodents
The Journal of clinical investigation, 2008Co-Authors: Yuki Takayanagi, Shuji Hinuma, Shoji Fukusumi, Hirokazu Matsumoto, Toshihiko Yada, Takashi Mera, Gareth Leng, Masanori Nakata, Yoichi Ueta, Tatsushi OnakaAbstract:Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express Prolactin-Releasing Peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this Peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating Peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.
-
Downregulation of Prolactin-Releasing Peptide gene expression in the hypothalamus and brainstem of diabetic rats.
Peptides, 2007Co-Authors: Takashi Mera, Tatsushi Onaka, Hiroaki Fujihara, Makoto Kawasaki, Hirofumi Hashimoto, Jun Saito, Takeshi Saito, Minori Shibata, Yoshiya Tanaka, Takakazu OkaAbstract:We investigated the Prolactin-Releasing Peptide (PrRP) mRNA levels in the hypothalamus and brainstem of streptozotocin (STZ)-induced diabetic rats and fa/fa Zucker diabetic rats, using in situ hybridization histochemistry. PrRP mRNA levels in the hypothalamus and brainstem of STZ-induced diabetic rats were significantly reduced in comparison with those of control rats. PrRP mRNA levels in the diabetic rats were reversed by both insulin and leptin. PrRP mRNA levels in the fa/fa diabetic rats were significantly reduced in comparison with those of Fa/? rats. PrRP mRNA levels in the fa/fa diabetic rats were significantly increased by insulin-treatment, but did not reach control levels in the Fa/? rats. We also investigated the effect of restraint stress on PrRP mRNA levels in STZ-induced diabetic rats. The PrRP mRNA levels in the control and the STZ-induced diabetic rats increased significantly after restraint stress. The diabetic condition and insulin-treatment may affect the regulation of PrRP gene expression via leptin and other factors, such as plasma glucose level. The diabetic condition may not impair the role of PrRP as a stress mediator.
Kinji Inoue - One of the best experts on this subject based on the ideXlab platform.
-
Stress Response of Prolactin‐Releasing Peptide Knockout Mice as to Glucocorticoid Secretion
Journal of neuroendocrinology, 2010Co-Authors: Akikazu Mochiduki, T. Takeda, S. Kaga, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion.
-
Prolactin-Releasing Peptide regulates the cardiovascular system via corticotrophin-releasing hormone.
Journal of neuroendocrinology, 2009Co-Authors: T. Yamada, Akikazu Mochiduki, Y. Sugimoto, Y. Suzuki, Keiichi Itoi, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP)-producing neurones are known to be localised mainly in the medulla oblongata and to act as a stress mediator in the central nervous system. In addition, central administration of PrRP elevates the arterial pressure and heart rate. However, the neuronal pathway of the cardiovascular effects of PrRP has not been revealed. In the present study, we demonstrate that PrRP-immunoreactive neurones projected to the locus coeruleus (LC) and the paraventricular nucleus (PVN) of the hypothalamus. The c-fos positive neurones among the noradrenaline cells in the LC, and the parvo- and magnocellular neurones in the PVN, were increased after central administration of PrRP. The arterial pressure and heart rate were both elevated after i.c.v. administration of PrRP. Previous studies have demonstrated that PrRP stimulated the neurones in the PVN [i.e. oxytocin-, vasopressin- and corticotrophin-releasing hormone (CRH)-producing neurones], which suggests that PrRP may induce its cardiovascular effect via arginine vasopressin (AVP) or CRH. Although the elevation of blood pressure and heart rate elicited by PrRP administration were not inhibited by an AVP antagonist, they were completely suppressed by treatment with a CRH antagonist. Thus, we conclude that PrRP stimulated CRH neurones in the PVN and that CRH might regulate the cardiovascular system via the sympathetic nervous system.
-
Prolactin-Releasing Peptide
Encyclopedia of Neuroscience, 2009Co-Authors: Akikazu Mochiduki, Sukumar Devnath, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) is found as an endogenous ligand of G-protein-coupled receptor (hGR3/UHR-1/GPR10) which is highly expressed in the anterior pituitary gland. PrRP and PrRP receptor mRNA are expressed in the brain and some peripheral tissues. In addition, PrRP positive neurons are localized in A1 and A2 noradrenalin cells in the medulla oblongata and in the dorsomedial nucleus of the hypothalamus. In addition to prolactin release, PrRP has various functions in the central nervous system, such as regulating the hypothalamic–pituitary–adrenal axis and mediating stress responses, food intake regulation, blood pressure, and the opioid system.
-
Appearance of Prolactin-Releasing Peptide-producing cells in the area postrema of postnatal rats.
Regulatory Peptides, 2007Co-Authors: Ken Fujiwara, Kimie Usui, Takashi Yashiro, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) was recently isolated from bovine hypothalamus. PrRP is the natural ligand for an orphan G-protein-coupled receptor, hGR3, and directly stimulates prolactin secretion from the anterior pituitary in vitro and in vivo. It has also been reported that PrRP plays an important role as a neurotransmitter and/or neuromodulator in the brain. Although much knowledge has been gained concerning PrRP in the adult rat brain, little attention has been paid to the fetal and postnatal stages. We therefore examined the development of PrRP neurons in the rat brain. In immunocytochemical and in situ hybridization experiments, we observed the transient appearance of PrRP-producing cells in the area postrema (AP), in which PrRP-producing cells do not exist in the normal adult rat. PrRP-producing cells in the AP were detected at P14, and many PrRP-producing cells were observed at P17, though none were detected at P19. This is the first report of the appearance of PrRP-producing cells in the postnatal AP. Our findings suggest that PrRP may play a previously unknown role in the AP of postnatal rats.
-
Physiological roles of Prolactin-Releasing Peptide.
Regulatory Peptides, 2005Co-Authors: Ken Fujiwara, Sachika Adachi, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) was first isolated from bovine hypothalamus as an orphan G-protein-coupled receptor using the strategy of reverse pharmacology. The initial studies showed that PrRP was a potent and specific Prolactin-Releasing factor. Morphological and physiological studies, however, indicated that PrRP may play a wide range of roles in neuroendocrinology other than prolactin release, i.e., metabolic homeostasis, stress responses, cardiovascular regulation, gonadotropin secretion, GH secretion and sleep regulation. This review will provide the current knowledge of PrRP, especially its roles in energy metabolism and stress responses.
Shuji Hinuma - One of the best experts on this subject based on the ideXlab platform.
-
Endogenous Prolactin-Releasing Peptide regulates food intake in rodents
The Journal of clinical investigation, 2008Co-Authors: Yuki Takayanagi, Shuji Hinuma, Shoji Fukusumi, Hirokazu Matsumoto, Toshihiko Yada, Takashi Mera, Gareth Leng, Masanori Nakata, Yoichi Ueta, Tatsushi OnakaAbstract:Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express Prolactin-Releasing Peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this Peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating Peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.
-
Appearance of Prolactin-Releasing Peptide-producing neurons in the area postrema of adrenalectomized rats.
Neuroscience letters, 2003Co-Authors: Ken Fujiwara, Shuji Hinuma, Chieko Kitada, Hirokazu Matsumoto, Minoru Maruyama, Kimie Usui, Takafumi Sakai, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) was found to be a novel hypothalamic Peptide that stimulates prolactin release in vitro and in vivo. In the normal adult rat brain, PrRP neurons are known to be located in only three areas, i.e. the dorsomedial hypothalamic nucleus, ventrolateral reticular formation; and nucleus of the tractus solitarius in the medulla oblongata. These PrRP neurons project neurites into various brain areas, including regions such as the paraventricular nucleus, supraoptic nucleus, and bed nucleus of the stria terminalis. Both PrRP nerve fibers and a high level of PrRP receptor, UHR-1, mRNA are observed in the area postrema (AP),but no PrRP neurons are detected in the AP of normal rats. In this study, we clearly demonstrated that PrRP-producing cells newly appeared in the AP of adrenalectomized rats by in situ hybridization and immunocytochemistry. Our results suggest that PrRP may have some important roles in the AP of adrenalectomized rats. This is the first report demonstrating the appearance of PrRP-positive cells in the AP.
-
Effects of Prolactin-Releasing Peptide microinjection into the ventrolateral medulla on arterial pressure and sympathetic activity in rats.
Brain research, 2002Co-Authors: Jouji Horiuchi, Shuji Hinuma, Shigenobu Kanba, Takeshi Saigusa, Nobuhiro Sugiyama, Yasuhiro Nishida, Yu Sato, Jun AritaAbstract:Prolactin-Releasing Peptide (PrRP), originally isolated from the hypothalamus, is highly localized in the cardiovascular regions of the medulla, and intracerebroventricular administration of PrRP causes a pressor response. In the present study we investigated the cardiovascular effects of PrRP applied to functionally different areas of the ventrolateral medulla (VLM), and to the nucleus tractus solitarius (NTS) and the area postrema (AP). In urethane-anesthetized rats, microinjection of PrRP into the pressor area of the most caudal VLM, recognized as the caudal pressor area in the rat, elicited dose-dependent increases in mean arterial pressure, heart rate, and renal sympathetic nerve activity. In the same injection area, neither thyrotropin-releasing hormone, corticotropin-releasing hormone nor angiotensin II affected these baseline cardiovascular variables. On the other hand, microinjection of PrRP into more rostral parts of the VLM, i.e. the depressor area of the caudal VLM and the pressor area of the rostral VLM, as well as the NTS and the AP, had no effect on these cardiovascular variables. Immunohistochemical analysis in the medulla revealed that the cardiovascularly PrRP-responsive region contained PrRP-immunoreactive cell bodies and nerve fibers. These results suggest that the most caudal VLM is an action site of PrRP to induce a pressor response, which is mediated, at least partly, by the increase in sympathetic outflow.
-
Stimulation of corticotropin-releasing hormone-mediated adrenocorticotropin secretion by central administration of Prolactin-Releasing Peptide in rats
Neuroscience letters, 2000Co-Authors: Hirokazu Matsumoto, Ken Fujiwara, Shuji Hinuma, Chieko Kitada, Haruo Onda, Osamu Nishimura, Minoru Maruyama, Jiro Noguchi, Yasuko Horikoshi, Kinji InoueAbstract:Prolactin-Releasing Peptide (PrRP) is a recently isolated hypothalamic Peptide which is an endogenous ligand to an orphan receptor. We previously demonstrated that PrRP neurons are widely distributed throughout the rat brain and suggested that PrRP may have important functions in the central nervous system. To analyze the function of PrRP, we studied the effect of intracerebroventricular (i.c.v.) PrRP administration on c-Fos protein accumulation in the rat brain. The results clearly indicated that c-Fos protein accumulation was dramatically increased in the nuclei of corticotropin-releasing hormone (CRH)-positive parvocellular neurosecretory cells in the paraventricular nucleus (PVN). We also demonstrated synapse-like contact between PrRP neurons and CRH cell bodies in the PVN, which suggests that PrRP31 has some effect on CRH secretion. We therefore investigated the effect of i.c.v. administration of PrRP31 on the CRH-mediated increase in adrenocorticotropin (ACTH) levels, and found that plasma ACTH levels were indeed increased by i.c.v. PrRP31. In addition, animals pre-treated with intravenous α-helical CRH, a potent CRH antagonist, showed attenuated plasma ACTH responses after i.c.v. PrRP31 administration. These results strongly suggest that PrRP affects the hypothalamic-pituitary-adrenal axis.
-
Analyses for susceptibility of rat anterior pituitary cells to Prolactin-Releasing Peptide.
Endocrine, 2000Co-Authors: Yuji Kawamata, Shuji Hinuma, Yugo Habata, Ryo Fujii, Masaki Hosoya, Shoji Fukusumi, Chieko Kitada, Haruo Onda, Osamu Nishimura, Masahiko FujinoAbstract:We validated the effect of Prolactin-Releasing Peptide (PrRP) on prolactin (PRL) secretion from rat anterior pituitary cells in in vitro culture. We found that culture conditions considerably influenced the response of the anterior pituitary cells to PrRP. Longer culture term (4 d) was required to obtain better responses of the anterior pituitary cells to PrRP in comparison to thyrotropin-releasing hormone (TRH). Under the culture conditions employed here, PrRP was comparable to TRH in the potency promoting PRL secretion, and the action of PrRP was very specific for PRL secretion. The susceptibility of the anterior pituitary cells to PrRP varied in female rats depending on the process of reproduction: the cells prepared from lactating rats were the most sensitive to PrRP compared with those from random-cycle and pregnant rats. Because the expression levels of PrRP receptor mRNA in the pituitary varied during the reproductive process, we speculated that the susceptibility of the anterior pituitary cells would reflect cellular changes including the expression level of PrRP receptors. In addition, treatment with estrogen in vivo enhanced the susceptibility of the cultured anterior pituitary cells in male rats. Our results indicate that the susceptibility of the rat anterior pituitary cells to PrRP is regulated by physiological mechanisms.
Simon M Luckman - One of the best experts on this subject based on the ideXlab platform.
-
Prolactin-Releasing Peptide Mediates Cholecystokinin-Induced Satiety in Mice
Endocrinology, 2006Co-Authors: David A. Bechtold, Simon M LuckmanAbstract:We have shown previously that Prolactin-Releasing Peptide (PrRP) plays a role in the regulation of feeding and energy expenditure in rats. We hypothesize that PrRP may have a physiological action through its putative receptor, GPR10, to mediate the central anorexigenic effects of peripheral satiety factors. Here we examine the effects of PrRP and cholecystokinin (CCK) on feeding in mice, including PrRP receptor gene knockout animals (GPR10(-/-)). Intracerebroventricular administration of PrRP (1-4 nmol) inhibited feeding in C57B6/J mice under both fast-induced and nocturnal feeding conditions. In contrast to the observations made in wild-type mice, neither PrRP nor CCK reduced food intake in GRP10(-/-) mice. The reduction in feeding and the release of corticosterone induced by systemic injection of the stressor lipopolysaccharide was similar in both GPR10(+/+) and GPR10(-/-) mice. These findings suggest that PrRP, acting through GPR10, is involved in regulating food intake and may be a key intermediary in the central satiating actions of CCK.
-
Characterization of a naturally-occurring polymorphism in the UHR-1 gene encoding the putative rat Prolactin-Releasing Peptide receptor
Peptides, 2005Co-Authors: Kate L. J. Ellacott, Emma Donald, John Edward Norris Morten, Dave J. Masters, John Brennand, Paul Clarkson, Simon M LuckmanAbstract:Abstract The rat orphan receptor UHR-1 and its human orthologue, GPR10, were first isolated in 1995. The ligand for this receptor, Prolactin-Releasing Peptide (PrRP), was identified in 1998 by reverse pharmacology and has subsequently been implicated in a number of physiological processes. As supported by its localization and regulation in the hypothalamus and brainstem, we have shown previously that PrRP is involved in energy homeostasis. Here we describe a naturally occurring polymorphism in the UHR-1 gene that results in an ATG to ATA change at the putative translational initiation site. The presence of the polymorphism abolished the binding of 125I PrRP in rat brain slices but did not affect the ability of PrRP to reduce fast-induced food intake. Together this data suggest that PrRP may be exerting its feeding effects through a receptor other than UHR-1.
-
Anorectic actions of Prolactin-Releasing Peptide are mediated by corticotropin-releasing hormone receptors
American journal of physiology. Regulatory integrative and comparative physiology, 2003Co-Authors: Catherine B. Lawrence, Yong Ling Liu, Michael J. Stock, Simon M LuckmanAbstract:Prolactin-Releasing Peptide (PrRP) reduces food intake and body weight and modifies body temperature when administered centrally in rats, suggesting a role in energy homeostasis. However, the media...
-
Repeated administration of the anorectic factor Prolactin-Releasing Peptide leads to tolerance to its effects on energy homeostasis.
American journal of physiology. Regulatory integrative and comparative physiology, 2003Co-Authors: Kate L. J. Ellacott, Catherine B. Lawrence, Lynn E. Pritchard, Simon M LuckmanAbstract:Central administration of a single dose of Prolactin-Releasing Peptide (PrRP) causes a reduction in both fast-induced and nocturnal food intake and body weight gain. The aim of this study was to examine the effect of repeated administration of PrRP on energy homeostasis, including a measure of the expression of the mitochondrial uncoupling protein-1 (UCP-1) in brown adipose tissue. Conscious, free-feeding animals received central injections of PrRP (4 nmol icv) or vehicle. A single injection at 1000 caused a sustained hyperthermia over the 4-h test period and an increase in the expression of UCP-1 mRNA. Repeated, twice daily injection caused a reduction in body weight gain greater than that seen in pair-fed animals for the first 48-72 h. After 72 h, the animals became refractory to the actions of PrRP. The pair-fed group showed a reduction in UCP-1 mRNA expression at 48 h, which was reversed by PrRP treatment. This study indicates that PrRP exerts its effects on energy homeostasis in the short-medium term by reducing food intake and increasing energy expenditure.
-
Alternative role for Prolactin-Releasing Peptide in the regulation of food intake
Nature Neuroscience, 2000Co-Authors: Catherine B. Lawrence, John Brennand, Fulvio Celsi, Simon M LuckmanAbstract:Prolactin-Releasing Peptide (PrRP) is a Peptide ligand for the human orphan G-protein-coupled receptor hGR3/GPR10 and causes the secretion of prolactin from anterior pituitary cells^ 1 . However, the lack of immunoreactive staining for PrRP in the external layer of the median eminence seems to rule out this Peptide as a classical hypophysiotropic hormone^ 2 , 3 , 4 and, furthermore, PrRP is less effective than another inducer of prolactin secretion, thyrotropin-releasing hormone, both in vitro and in vivo ^ 5 , 6 , 7 . Here we show a reduction in the expression of PrRP mRNA during lactation and fasting and an acute effect of PrRP on food intake and body weight, supporting the hypothesis of an alternative role for the Peptide.
