Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the recent progress in the understanding of the neurobiology of the eating disorders. The analysis of the biochemical abnormalities present in the patients with bulimia nervosa indicates the decrease of central serotonin and noradrenalin activity, elevation of the levels of cerebrospinal fluid peptide YY, alterations of the endogenous opioids and also reduction of peripheral cholecystokinin levels. As these studies were performed on patients who were actively binging and purging it is conceivable that the above abnormalities can results from a pathological feeding pattern. It is also suggested that the reduction of central serotoninergic activity is the stable, trait-related dysregulation of neurotransmitter system activity. In patients with anorexia nervosa the endocrine disturbances of the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes were thoroughly studied. Underweight anorectic patients have been found to have elevations of cerebrospinal fluid level of neuropeptide Y, corticotropin releasing hormone and vasopressin as well as reductions of beta-endorphin and oxytocin level. However, most of the neuropeptide alterations normalize following weight recovery. The only exception is a persistent increase of central serotonin activity postulated to be responsible for the obsessive-compulsive personality traits and disturbed eating behaviors found in these patients.
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PMID:[Selected issues of biological aspects of eating disorders]. 799 11

The possible cooperation of neuropeptide Y (NPY) and alpha-1-adrenergic mechanisms in the release of oxytocin (OT) in conscious, nonsuckled lactating rats was examined following microinjections of NPY and its analogs and/or alpha-adrenergic drugs into the supraoptic nucleus (SON) or anterior paraventricular nucleus/anterior commissural nucleus (PVN/ACN). The alpha-1-adrenergic agonist phenylephrine dose dependently increased plasma OT after injection into the SON or the PVN/ACN, and this was prevented by treatment with the specific alpha-alpha-1-adrenergic receptor antagonist prazosin, but not by the alpha-2 antagonist rauwolscine. The alpha-2-adrenergic agonist clonidine did not increase plasma OT. Injection of NPY or of the related peptide YY (PYY) alone into the SON or the PVN/ACN also dose dependently increased plasma OT; this was also significantly attenuated by prazosin. Plasma OT responses to NPY and PYY differed significantly in dynamics and duration, which may be related to large differences found in the patterns of displaceable binding of [125I]NPY and [125I]PYY to hypothalamic membranes. The stimulatory action of NPY was mimicked by a preferential Y-1 receptor agonist, but not by an agonist of the Y-2 NPY receptor. Coinjection of NPY or PYY and phenylephrine into either the SON or the PVN/ACN area produced a greater than additive discharge of OT, especially in the SON. This increase was mostly due to a markedly enhanced initial release of OT, and was also completely eliminated by prazosin. The NPY-alpha-1 interaction in stimulating plasma OT was not mediated by direct binding of the peptides to alpha-1-adrenergic receptor sites. These results indicate that 1) the stimulatory noradrenergic influence on OT secretion in the lactating rat is mediated by the alpha-1 adrenergic receptor via an action in the PVN/ACN and SON; 2) NPY also stimulates OT secretion in the lactating rat through the Y-1 receptor subtype in the PVN/ACN and SON; 3) NPY markedly enhances the OT secretory responses to alpha-1 receptor stimulation, particularly in the SON. The cooperative stimulation by NE and NPY may be of physiological importance in mediating the episodic release of OT in response to suckling.
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PMID:Central stimulation of oxytocin release in the lactating rat: interaction of neuropeptide Y with alpha-1-adrenergic mechanisms. 838 Oct 69

Neuropeptide Y and peptide YY are important central and peripheral modulators of cardiovascular and neuroendocrine functions, that act through multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand-binding studies in isolated nerve terminals from the rat neurohypophysis. Functionally, neuropeptide Y and peptide YY dose-dependently triggered arginine 8-vasopressin and oxytocin release from perfused isolated terminals, and potentiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days caused a more than three-fold increase in the neuropeptide Y content of the nerve endings. However, the Y2 receptor expression and arginine-8-vasopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-vasopressin release by neuropeptide Y may not be explained by neuropeptide Y effects on intracellular Ca2+. First, absence of Ca2+ from the perfusion medium did not affect the arginine-8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentrations. Pretreatment with pertussis toxin blocked arginine-8-vasopressin secretion by neuropeptide Y, suggesting activation of Gi or Go heterotrimeric G-proteins are required for secretion. It is concluded, that the nerve endings of the neurohypophysis contain a complete neuropeptide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to stimulate the release of vasopressin and oxytocin via a Gi/Go dependent secretory mechanism.
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PMID:Neuropeptide Y2 receptors on nerve endings from the rat neurohypophysis regulate vasopressin and oxytocin release. 948 7

Neuropeptides play an important role in the regulation of feeding behavior and obesity. The mechanisms for controlling food intake involve a complicated interplay between peripheral systems (including gustatory stimulation, gastrointestinal peptide secretion, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monamines (serotonin, dopamine, norepinephrine). In addition to regulating eating behavior, a number of CNS neuropeptides participate in the regulation of neuroendocrine pathways. Thus, clinical studies have evaluated the possibility that CNS neuropeptide alterations may contribute to dysregulated secretion of the gonadal hormones, cortisol, thyroid hormones and growth hormone in the eating disorders. Most of the neuroendocrine and neuropeptide alterations apparent during symptomatic episodes of AN and BN tend to normalize after recovery. This observation suggests that most of the disturbances are consequences rather than causes of malnutrition, weight loss and/or altered meal patterns. Still, an understanding of these neuropeptide disturbances may shed light on why many people with AN or BN cannot easily "reverse" their illness and even after weight gain and normalized eating patterns, many individuals who have recovered from AN or BN have physiological, behavioral and psychological symptoms that persist for extended periods of time.
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PMID:A review of neuropeptide and neuroendocrine dysregulation in anorexia and bulimia nervosa. 1276 12

Anorexia and Bulimia Nervosa are disorders of unknown etiology that invariably begin during adolescence and near in time to puberty in young women. These disorders are associated with aberrant eating behaviors, body image distortions, impulse and mood disturbances, as well as characteristic temperament and personality traits. It is well known that malnutrition produces changes in neuroendocrine function. More recently, disturbances in neuronal systems have been found to play a role in the modulation of feeding, mood, and impulse control. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monoamines (serotonin, dopamine, norepinephrine). Disturbances of most of these neuronal systems have been found when people are ill with an eating disorder, but it was not certain whether they were a cause or consequence of symptoms. In order to address these questions, a growing number of studies have investigated whether neuromodulatory disturbances persist after recovery. Studies from several centers tend to show altered serotonin activity persists after prolonged normalization of weight, nutrition, and menstrual function, as do anxiety, obsessionality, and perfectionism. While there are fewer data, there may be persistent alterations of dopamine or some neuropeptides in some subjects in a recovered state. The inaccessibility of the central nervous system has made it difficult to understand brain and behavior. In the past decade, new tools, such as brain imaging, have offered the possibility of better characterization of complex neuronal function and behavior. Such studies have tended to consistently find that alterations of brain regions, such as the temporal lobe, occur in people who are ill with anorexia nervosa and appear to persist after some degree of weight gain and recovery. New imaging technology, that marries Positron Emission Tomography (PET) imaging with selective neurotransmitter radioligands, confirms that altered serotonin neuronal pathway activity persists after recovery from an eating disorder and supports the possibility that these psychobiological alterations might contribute to traits, such as increased anxiety or extremes of impulse control, that, in turn, may contribute to a vulnerability to the development of an eating disorder. In summary, studies of pathophysiology are starting to nominate new candidates for treatment leading to the possibility of finding effective treatments for this often chronic or fatal disorder.
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PMID:Neurotransmitter and imaging studies in anorexia nervosa: new targets for treatment. 1276 13

Obesity is a major global epidemic, with over 300 million obese people worldwide, and nearly 1 billion overweight adults. Being overweight carries significant health risks, reduced quality of life, and impaired socioeconomic success, with profound consequences for health expenditure. The most successful treatment for obesity is gastric bypass surgery, which acts in part by reducing appetite through alterations in gut hormones. Circulating gut hormones, secreted or suppressed after eating food, act in the brain, particularly the hypothalamus, to alter hunger and fullness. Stomach-derived ghrelin increases food intake even in those with anorexia from chronic illness, while pancreatic polypeptide (PP), intestinal peptide YY 3-36 (PYY), oxyntomodulin, and other hormones reduce food intake and appetite. While obese subjects have appropriate reductions in orexigenic ghrelin, other gut-hormone disturbances may contribute to obesity such as reduced anorexigenic PYY and PP. Prader-Willi syndrome (PWS) arises from the loss of paternally inherited genes on chromosome 15q11-13, leading to life-threatening insatiable hunger and obesity from early childhood, through developmental brain, particularly hypothalamic defects. The study of genetically homogenous causes of abnormal-feeding behavior helps our understanding of appetite regulation. PWS subjects have inappropriately elevated plasma ghrelin for their obesity, at least partly explained by preserved insulin sensitivity. It remains unproven if their hyperghrelinemia or other gut-hormone abnormalities contribute to the hyperphagia in PWS, in addition to brain defects. Postmortem human hypothalamic studies and generation of animal models of PWS can also provide insight into the pathophysiology of abnormal-feeding behavior. Changes in orexigenic NPY and AGRP hypothalamic neurons, or anorexigenic oxytocin neurons have been found in illness and PWS. Functional neuroimaging studies, using PET and fMRI, will also allow us to tease apart the hormonal and brain pathways responsible for controlling human appetite, and their defects in obesity.
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PMID:The hypothalamus, hormones, and hunger: alterations in human obesity and illness. 1687 68

Appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion. Peripheral regulation includes satiety signals and adiposity signals, while central control is accomplished by several effectors, including the neuropeptidergic, monoaminergic and endocannabinoid systems. Satiety signals, including cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), originate from the gastrointestinal (GI) tract during a meal and, through the vagus nerve, reach the nucleus tractus solitarius (NTS) in the caudal brainstem. From NTS afferents fibers project to the arcuate nucleus (ARC), where satiety signals are integrated with adiposity signals, namely leptin and insulin, and with several hypothalamic and supra-hypothalamic inputs, thus creating a complex network of neural circuits which finally elaborate the individual response to a meal. As for the neuropeptidergic system, ARC neurons secrete orexigenic substances, such as neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic peptides such as pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Other brain areas involved in the control of food intake are located downstream the ARC: among these, the paraventricular nucleus (PVN), which produces anorexigenic peptides such as thyrotropin releasing hormone (TRH), corticotrophin releasing hormone (CRH) and oxytocin, the lateral hypothalamus (LHA) and perifornical area (PFA), secreting the orexigenic substances orexin-A (OXA) and melanin concentrating hormone (MCH). A great interest in endocannabinoids, important players in the regulation of food intake, has recently developed. In conclusion, the present work reviews the most recent insights into the complex and redundant molecular mechanisms regulating food intake, focusing on the most encouraging perspectives for the treatment of obesity.
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PMID:Neuroendocrine control of food intake. 1806 14

Because obesity is a risk factor for many serious illnesses such as diabetes, better understandings of obesity and eating disorders have been attracting attention in neurobiology, psychiatry, and neuroeconomics. This paper presents future study directions by unifying (i) economic theory of addiction and obesity [4-6], and (ii) recent empirical findings in neuroeconomics and neurobiology of obesity and addiction. It is suggested that neurobiological substrates such as adiponectin, dopamine (D2 receptors), endocannabinoids, ghrelin, leptin, nesfatin-1, norepinephrine, orexin, oxytocin, serotonin, vasopressin, CCK, GLP-1, MCH, PYY, and stress hormones (e.g., CRF) in the brain (e.g., OFC, VTA, NAcc, and the hypothalamus) may determine parameters in the economic theory of obesity. Also, the importance of introducing time-inconsistent and gain/loss-asymmetrical temporal discounting (intertemporal choice) models based on Tsallis' statistics and incorporating time-perception parameters into the neuroeconomic theory is emphasized. Future directions in the application of the theory to studies in neuroeconomics and neuropsychiatry of obesity at the molecular level, which may help medical/psychopharmacological treatments of obesity (e.g., with sibutramine), are discussed.
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PMID:Toward molecular neuroeconomics of obesity. 2046 3

Although active learning works, promoting it in large undergraduate science classes is difficult. Here, three students (F. Naji, L. Salci, and G. Hoit) join their teacher (P. K. Rangachari) in describing one such attempt. Two cohorts in a first-year undergraduate biology course explored the molecular underpinnings of human misbehavior. Students were divided into 18 groups and randomly allotted to deal with one of the four deadly sins: sloth, gluttony, lust, and wrath. Students were expected to read primary sources to devise molecular ways to counter these sins. Group progress was monitored over the 12-wk period by the preceptor (P. K. Rangachari) at scheduled intervals. A single randomly selected student was questioned about the work done, and future directions were provided by the preceptor. At the end of the term, randomly selected students defended their group's approaches to the entire class. A final written report was graded. The following multiple target molecules were considered for each sin: gluttony (cholecystokinin, ghrelin, GABA, leptin, peptide YY, neuropeptide Y, and the melanocortin 4 receptor); sloth (dopamine, glutamate, GABA, and orexin); wrath (serotonin, GABA, glutamate, and corticotropin-releasing hormone receptor 2); and lust (prolactin, testosterone, oxytocin, dopamine, and estrogen). Students noted that the project provided a valuable learning experience, and the random selection approach gave students a greater sense of responsibility to their group. The project helped students hone their skills at searching, synthesizing, sharing, and presenting information, fostered group interactions, and provided a solid knowledge base for subsequent courses.
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PMID:The UNSIN project: exploring the molecular physiology of sins. 2238 7

Abstract Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanisms.
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PMID:Neuroendocrine control of satiation. 2539 24


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