Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to compare the effects of a pharmacologically induced decrease in body core temperature to the effects observed with lowering of body temperature by exposure to a cold environment. Our special interest was the involvement of 5-HT in thermoregulatory responses. Sixty healthy male volunteers were randomly assigned to one of the following conditions: exposure to normal ambient temperature (28 degrees C) and placebo, exposure to cold ambient temperature (5 degrees C) and placebo, or normal ambient temperature and 10 mg of the partial 5-HT1A agonist ipsapirone. As indicators of physiological responses to lowering of body temperature, tympanic temperature, skin temperature, EMA, metabolic rate, and heart rate were monitored and saliva cortisol levels and peripheral 5-HT concentrations were determined. In addition, ratings on ambient temperature, thermal discomfort, and feelings of irritability were obtained. While lowering of body core temperature was associated with marked counterregulations (decrease of skin temperature, increase in EMA and metabolic rate) and feelings of discomfort, this was not observed with ipsapirone. An increase in cortisol levels was primarily observed in the ipsapirone group and was not reflected by respective changes in whole blood or platelet 5-HT indicating that brain and platelet 5-HT are not related.
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PMID:Lowering of body core temperature by exposure to a cold environment and by a 5-HT1A agonist: effects on physiological and psychological variables and blood serotonin levels. 825 8

Migraine is regarded as a polygenic disease and serotonergic pathways appear to play a major role in its pathogenesis. In the present study, the role of the 5-HT1A and 5-HT1B receptors in migraine was evaluated. The human 5-HT1A receptor gene transcription is modulated by a functional C-1019G promoter polymorphism. The 5-HT1B receptor is the main effector of vasoconstriction in meningeal and cerebral arteries and its functional G861C promoter polymorphism was investigated. We report a positive association of the GG genotype of the 5-HT1A promoter polymorphism with avoidance of physical activity during a migraine attack in comparison to the CC genotype (p = 0.008). Moreover, a positive association of the CC genotype of the G861C polymorphism of the 5-HT1B receptor with the reported intensity of the headache attack on the visual analogue scale was observed (CC 8.3 +/- 1.5 vs. GG 6.9 +/- 1.8; p < 0.05). An association of either polymorphism with migraine with or without aura could not be found. For the first time, our results indicate a role of allelic variation of the 5-HT1A receptor in motion related discomfort in migraineurs and a role of the 5-HT1B receptor polymorphism in headache intensity.
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PMID:Functional polymorphisms of the 5-HT1A and 5-HT1B receptor are associated with clinical symptoms in migraineurs. 1741 40

The influence of acute and chronic (14 days) buspirone administration (1 mg/kg, intraperitoneally) on the behavior of C57BL/6J female mice, being in social discomfort, were studied. The conditions of social discomfort include the permanent habitation of females in the cage with aggressive males through a perforated partition and daily presence during intermale confrontations. The dynamic changes of 5-HT1A-receptor sensitivity in the brain of female mice, estimated by the female behavior after 30 min ofbuspirone administration, were discovered. The sensitivity increased at the early stages of pathological behavior development (10 days) and decreased after 20-30 days. Females who had reduced of 5-HT1A receptor sensitivity after 30 day of maintenance in social discomfort conditions also showed a decreased sensitivity on chronic buspirone administration.
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PMID:[Effects of buspirone on the behavior of female mice in a model of social discomfort]. 2301 7

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.
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PMID:Role of antispasmodics in the treatment of irritable bowel syndrome. 2487 26

Emotional stress is primarily triggered by the cognitive processing of negative input; it is regarded as a serious pathogenetic factor of depression that is challenging to model in animals. While available stress paradigms achieve considerable face and construct validity in modelling depressive disorders, broader use of naturalistic stressors instead of the more prevalent models with artificial challenges inducing physical discomfort or pain may substantially contribute to the development of novel antidepressants. Here, we investigated whether a 3-week exposure of Wistar rats and Balb/c mice to unpredictably alternating frequencies of ultrasound between the ranges of 20-25 and 25-45kHz, which are known to correspond with an emotionally negative and with a neutral emotional state, respectively, for small rodents in nature, can induce behavioural and molecular depressive-like changes. Both rats and mice displayed decreased sucrose preference, elevated "despair" behaviour in a swim test, reduced locomotion and social exploration. Rats showed an increased expression of SERT and 5-HT2A receptor, a decreased expression of 5-HT1A receptor in the prefrontal cortex and hippocampus, diminished BDNF on gene and protein levels in the hippocampus. Fluoxetine, administered to rats at the dose of 10mg/kg, largely precluded behavioural depressive-like changes. Thus, the here applied paradigm of emotional stress is generating an experimental depressive state in rodents, which is not related to any physical stressors or pain. In essence, this ultrasound stress model, besides enhancing animal welfare, is likely to provide improved validity in the modelling of clinical depression and may help advance translational research and drug discovery for this disorder.
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PMID:Ultrasound of alternating frequencies and variable emotional impact evokes depressive syndrome in mice and rats. 2703 99