Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recently developed device was used in a field study to continuously assess physical activity, heart rate, and cigarette lighting during 2 workdays and 2 days off in 12 female smokers and 12 female non-smokers. Heart rates did not differ between smokers and non-smokers or between workdays and days off; however, the nonsmokers showed significantly higher physical activity during the workdays. An averaging procedure used to obtain plots for smoking related changes of activity (SRA), pulse (SRP), and the pulse-activity ratio (SRpai) revealed four observations. a) "Lighting" responses consisting of parallel increases of SRA and SRP start a few minutes before lighting, reach a maximum with lighting, and drop immediately after lighting. b) The subsequent "smoking" responses last about 6 min and are characterized by a sustained postlighting SRA depression but immediate recovery of SRP, resulting in an increased SRpai level. c) Ten minutes prelighting and 10 min postlighting SRA and SRP are highly similar. d) The pattern of this response was similar for workdays and days off.
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PMID:Cigarette smoking related variation of heart rate and physical activity with ad libitum smoking under field conditions. 783 34

Corticotropin-releasing factor (CRF) and its related family members are implicated in stress-related disorders such as anxiety and depression. Recently, two new members of this neuropeptide family have been discovered in the brain: urocortin II (also known as stresscopin-related peptide) and urocortin III (also known as stresscopin). These urocortins are selective agonists for the CRF(2) receptor, show a distinct neuroanatomical localization and are involved in stress-coping responses such as anxiolysis. Thus, CRF, the urocortins and their receptors form an intricate network in the brain involved in the acute phase as well as the recovery phase of the stress response.
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PMID:Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. 1178 5

Abnormal signaling at corticotropin-releasing factor CRF1 and CRF2 receptors might contribute to the pathophysiology of stress-related disorders such as anxiety, depression and eating disorders, in addition to cardiac and inflammatory disorders. Recently, molecular characterization of CRF1 and CRF2 receptors and the cloning of novel ligands--urocortin, stresscopin-related peptide/urocortin II, and stresscopin/urocortin III--have revealed a far-reaching physiological importance for the family of CRF peptides. Although the physiological roles of the CRF2 receptor remain to be defined, the preclinical and clinical development of specific small-molecule antagonists of the CRF1 receptor opens new avenues for the treatment of psychiatric and neurological disorders.
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PMID:The CRF peptide family and their receptors: yet more partners discovered. 1183 Feb 63

1. The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF(1)) and 2 (CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF(1) receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2. Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3. Nonselective CRF(1)/CRF(2) antagonists and selective CRF(1) antagonists inhibit exogenous (central or peripheral) CRF- and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF(2) antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4. These findings implicate CRF(1) receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF(1)-dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders.
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PMID:CRF1 receptor signaling pathways are involved in stress-related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. 1510 Jan 65

Hypothalamic CRF plays a central role in the coordination of endocrine and behavioral responses to stress and it is also involved in the pathophysiology of several neuropsychiatric diseases including depression, anxiety and addiction. In the mammals, the CRF family of peptides includes CRF, urocortin (Ucn), Ucn I, and Ucn II while was enriched with new members, the urocortins. Their biological effects are mediated by the CRF1 and CRF2 receptors, which belong to the G-protein-coupled receptor super family. Multiple research groups have demonstrated during the last decade the expression of the CRF peptides and their receptors in several components of the immune system and their participation in the ad hoc regulation of inflammatory phenomena. Non-peptide CRF1 antagonists have been recently synthesized for the treatment of CNS related diseases, such as anxiety, depression and drug abuse. In the gastrointestinal tract, these compounds open new therapeutic options in the treatment of lower-GI inflammatory diseases associated to CRF, such as the chronic inflammatory bowel syndromes, irritable bowel disease and ulcerative colitis while Ucn, Ucn I, Ucn II or synthetic non-peptide CRF2 agonists may be useful in the treatment of upper-GI inflammatory diseases. In human endometrium, CRF1 antagonists may be used as abortive agents interfering with the inflammatory phenomena taking place during the implantation of the conceptus. They thus may represent a new class of nonsteroidal inhibitors of implantation. These two examples illustrate the potential therapeutic significance of the CRH in regulating inflammatory phenomena in an ad hoc approach without affecting the rest of the immune system.
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PMID:The corticotropin-releasing factor (CRF) family of neuropeptides in inflammation: potential therapeutic applications. 1597 83

The corticotropin-releasing factor (CRF)-like peptides, which include the mammalian peptides CRF, urocortin 1, urocortin 2, and urocortin 3, play an important role in orchestrating behavioral and physiological responses that may increase an organism's chance of survival when confronted with internal or external stressors. There is, however, evidence that a chronic overactivity of brain CRF systems under basal conditions may play a role in the etiology and maintenance of psychiatric disorders such as depression and anxiety disorders. In addition, there is evidence of a role for CRF-like peptides in acute and protracted drug abstinence syndromes and relapse to drug-taking behavior. This review focuses on the role of CRF-like peptides in the negative affective state associated with acute and protracted withdrawal from three widely abused drugs, cannabis, nicotine, and alcohol. In addition, we discuss the high comorbidity between stress-associated psychiatric disorders and drug dependence. A better understanding of the brain stress systems that may underlie psychiatric disorders, acute and protracted drug withdrawal, and relapse to drug-taking behavior may help in the development of new and improved pharmacotherapies for these widespread psychiatric disorders.
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PMID:The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. 1626 17

Most of the evidence suggests that corticotropin-releasing hormone (CRH) is involved in mood disorders. The CRF receptors type 1 (CRF(1) receptors) elicit a stress response, and their natural and synthetic antagonists have been studied as possible drugs against depression, whereas CRF receptors type 2 (CRF(2) receptors) appear to alleviate the stress response and mediate anxiolytic action. Other CRF family peptides are urocortin 1 (Ucn 1), urocortin 2 (Ucn 2) and urocortin 3 (Ucn 3). Little is known about the action of Ucn 1, Ucn 2 and Ucn 3 on depressive disorders. Antidepressant-like effects of Ucn 1, Ucn 2 and Ucn 3 (0.13, 0.25 and 0.5 microg/2 microl, i.c.v.) were assayed in mice in a modified forced swimming test (FST). This modified FST predicts the clinical efficacy of an antidepressant drug through the scoring of immobility, climbing and swimming behavior. The study demonstrated that Ucn 1 had no action on any of parameters studied in the modified FST. Ucn 2 elicited antidepressive-like action by shortening the immobility time. Additionally Ucn 2 significantly increased the climbing and swimming times. Ucn 3 likewise displayed an antidepressive-like effect by shortening the immobility time, and increasing the climbing and swimming times. The results suggest that CRF(2) receptor stimulation by Ucn 2 or Ucn 3 leads to antidepressant-like action, but dual stimulation of the CRF(1) and CRF(2) receptors by Ucn 1 does not trigger antidepressant-like action in the modified mouse FST.
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PMID:Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice. 1835 26

Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF(1) and CRF(2) receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF(1) receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF(1) receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF(1) receptor antagonists in blunting these stress-related components. The importance of CRF(1) signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients.
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PMID:From Hans Selye's discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: implication in stress-related functional bowel diseases. 1912 89

Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety- or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3 knock-out mice that were also present in male CRH-R2 knock-out mice. In conclusion, our results suggest a novel role for UCN3 and CRH-R2 related to the processing of social cues and to the establishment of social memories.
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PMID:Urocortin 3 modulates social discrimination abilities via corticotropin-releasing hormone receptor type 2. 2061 Jul 44

On the basis of extensive basic and clinical studies, corticotropin-releasing hormone (CRH) and its related family members are considered to play a pivotal role in stress-related disorders, such as anxiety and depression. CRH is regarded as the principal mediator in the brain of the stress response, as it mediates neuroendocrine, autonomic, and behavioral responses to stressful challenges. Recently, this neuropeptide family has expanded due to the discovery of two new members, urocortin II (also termed stresscopin-related peptide) and urocortin III (also termed stresscopin), which are selective agonists for the CRH receptor type 2. They show a discrete neuroanatomical localization and are involved in stress-coping responses, such as anxiolysis. Here, on the basis of recent developments, we suggest that CRH, the urocortins, and their receptors form a complex system in the brain, which is recruited during both the acute and the recovery phases of the stress response.
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PMID:On the role of corticotropin-releasing hormone receptors in anxiety and depression. 2203 45


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