Background-The purpose of this study was to investigate whether rats dosed with serotonin develop changes similar to those seen in human carcinoid heart disease. Methods and Results-Ten Sprague-Dawley rats were given serotonin injections subcutaneously once daily for 3 months; controls were given saline. A long-lasting hyperserotoninemia with a Ͼ10-fold increase in both platelet-poor plasma and dialysate from the femoral muscles appeared. The animals developed clinical signs such as flushing and loose stools. After 3 months, 6 of 10 rats given serotonin had pathological echocardiographs. Two animals had a combination of aortic and pulmonary valve insufficiency, 1 had isolated aortic valve insufficiency, and 3 had isolated pulmonary valve insufficiency. Histopathological examination revealed shortened and thickened aortic cusps and carcinoidlike plaques characterized by a collection of myofibroblasts within an extracellular matrix of collagen ground substance.Immunostaining for Ki-67 demonstrated an increased number of proliferating subendocardial cells. In the control group, no pathological changes were seen. With the use of reverse-transcription polymerase chain reaction, normal rat aortic cusps were shown to express mRNA for serotonin receptors 5-HT 1A , 5-HT 2A , and 5-HT 2B and the serotonin transporter 5-HTT. Conclusions-For the first time, long-term serotonin administration was performed in rats. Morphological and echocardiographic changes similar to those seen in human carcinoid heart disease developed. This study demonstrates that serotonin most likely is involved in the pathogenesis of carcinoid heart disease.
Recent studies have proposed a role for serotonin and its transporter in regulation of bone cell function. In the present study, we examined the in vitro effects of serotonin and the serotonin transporter inhibitor fluoxetine "Prozac" on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected the total number of differentiated osteoclasts as well as bone resorption in a bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also found in murine osteoblasts and osteoclasts, indicating an ability to produce serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine affected proliferation and NFkappaB activity in a biphasic manner. Proliferation of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A receptor expression was enhanced by serotonin. Fluoxetine stimulated proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations, microM concentrations were inhibitory. The effect of fluoxetine seemed direct, probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1 cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added. Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect. This study further describes possible mechanisms by which serotonin and the serotonin transporter can affect bone cell function.
Background: The Medical Student Research Programme is a national education and grant scheme for medical students who wish to carry out research in parallel with their studies. The purpose of the programme is to increase recruitment of people with a standard medical degree to medical research. The Research Programme was established in 2002 and underwent a thorough evaluation during the spring of 2007. The evaluation should investigate if the programme had fulfilled its objectives of increased recruitment to medical research, in addition to the students' and supervisors' satisfaction of the programme, and unwanted differences between the universities.
These findings show that serotonin may regulate adipocyte function in a direct manner via the blood circulation and/or paracrine and autocrine mechanisms, and not only indirectly via the CNS as previously assumed.
Background/Aim: Gastric bypass (GB) is usually designed to restrict food intake and to induce malabsorption. Gastric hormones have been thought to play a role in the regulation of food intake and body weight. The aim of the present study was to analyze feeding behavior after total gastrectomy (Gx) or GB in rats. Methods: Animals were subjected to Gx, GB, or sham operations. Eating and drinking behaviors after surgeries were assessed by a comprehensive laboratory animal monitoring system. Gastric hormones were measured by radioimmunoassay and energy density in feces by adiabatic bomb calorimeter. Results: Compared with sham operation, both Gx and GB reduced the body weight as measured during 3–8 weeks postoperatively, which was associated with increased energy expenditure per 100 g body weight. Daily accumulated food intake and meal size (during nighttime) were reduced following Gx, but not GB. The water intake (during daytime) was increased after Gx and GB. The energy density in feces was unchanged. Serum concentrations of ghrelin, obestatin, leptin, gastrin, and pancreastatin were greatly reduced after Gx. Conclusions: Control of food intake and meal size was independent of the food reservoir function of the stomach. Surgical depletion of gastric hormones is associated with reduced meal size, but increased water intake.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.