Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intravenous administration of 2-deoxy-D-glucose (2-DG) to conscious catheterised rats dose-dependently increased the levels of glucose in plasma throughout the analysis (60 min); the levels of insulin in plasma remained unchanged, except for an early significant decrease in rats treated with the largest dose (1 g/kg). Pretreatment (10 min beforehand) with the beta 2-adrenoceptor antagonist, ICI 118,551 (3 mg/kg) or the alpha 2-adrenoceptor antagonist, idazoxan (1 mg/kg) decreased the rise in levels of glucose in plasma elicited by 2-DG (250 mg/kg). Conversely, the alpha 1-adrenoceptor antagonist, prazosin (1 mg/kg) or the dopaminergic receptor blocker, haloperidol (0.5 mg/kg) amplified the hyperglycaemic response to 2-DG. Previous administration of either the 5-HT1A/5-HT2 receptor antagonist, spiperone (3 mg/kg), the 5-HT1/5-HT2 receptor antagonist, methysergide (1 mg/kg), the 5-HT1C/5-HT2 receptor antagonist, ritanserin (1 mg/kg) or the 5-HT3 receptor antagonist, ICS 205.930 (0.1 mg/kg) did not affect 2-DG-induced hyperglycaemia. On the other hand, the mixed 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, (-)-propranolol (5 mg/kg) and the 5-HT1/5-HT2 receptor antagonist, methiotepin (1 mg/kg), respectively, diminished and amplified the hyperglycaemia elicited by 2-DG. Lastly, in rats pretreated with prazosin (1 mg/kg, 30 min beforehand), an additional pretreatment (10 min beforehand) with prazosin or methiotepin (both at 1 mg/kg) did not further amplify the hyperglycaemic response to 2-DG. These results indicate that 2-DG-induced hyperglycaemia is mediated by alpha 2- and beta 2-adrenoceptors and amplified by alpha 1-adrenoceptor blockade. Conversely, neither 5-HT1, 5-HT2 nor 5-HT3 receptors played a role in the hyperglycaemic response to 2-DG.
 ...
PMID:Influence of catecholaminergic and serotonergic receptor antagonists on the hyperglycaemic response to the neuroglucopaenic agent, 2-deoxy-D-glucose. 165 2

Local cerebral glucose utilization following the acute administration of the 5-HT3 receptor antagonist ondansetron (0.01-1.0 mg/kg) was determined using [14C]2-deoxyglucose quantitative autoradiography. Ondansetron effected alterations in 13 of the 66 brain areas analyzed including limbic, auditory and visual structures. In the majority of these 13 regions ondansetron was only effective at reducing glucose use compared to control values at a dose of 0.01 mg/kg. Thus in limbic and related areas (CA2 and CA3 fields of the hippocampus, lateral habenula and septal nucleus) glucose utilization was reduced by 15-21%. Similar reductions (18-20%) were apparent in primary auditory and visual areas (auditory cortex, medial geniculate and visual cortex). However, with the exception of the ventromedial thalamic nucleus (14% reduction) glucose use in extrapyramidal and sensory motor areas was unchanged. Following larger doses of ondansetron (0.1 and 1.0 mg/kg), there was no change in cerebral glucose utilization relative to control values, with the exception of the median raphe. In this structure local cerebral glucose utilization was significantly increased (P less than 0.05) following administration of 1.0 mg/kg ondansetron relative to the lower dose of 0.01 mg/kg. Changes in glucose use did not always reflect areas of high 5-HT3 receptor density. Thus, although cerebral glucose use was reduced in hippocampal layers, it was unchanged in the entorhinal cortex and the area postrema. These data suggest that under these experimental conditions ondansetron produces modest changes in glucose utilization which are primarily confined to limbic structures and those involved in sensory processing.
 ...
PMID:Neuroanatomical structures involved in the action of the 5-HT3 antagonist ondansetron: a 2-deoxyglucose autoradiographic study in the rat. 182 59

The functional effects of serotonin (5-HT) drugs and toxins on regional cerebral metabolic rates for glucose (rCMRglc) have been determined in rats with the in vivo, quantitative, autoradiographic [14C]2-deoxyglucose technique. Serotonin agents produced rCMRglc patterns different and more specific that one would predict from binding studies. At low doses 5-HT1 agonists reduced rCMRglc in limbic areas and at high doses increased rCMRglc in brain motor regions. The 5-HT2 agonists dose-dependently decreased rCMRglc in proencephalic areas and increased it in thalamic nuclei. 5-HT3 receptor antagonism resulted in rCMRglc decreases in limbic, auditory and visual areas and agents with 5-HT3 receptor activity increased rCMRglc in brain regions with high 5-HT3 receptor densities. Serotonin anxiolytics (e.g. azapirones) and antidepressants (e.g. tryciclic and non-tryciclic 5-HT reuptake inhibitors) reduced rCMRglc selectively in limbic areas and in brainstem monoaminergic nuclei. Dose, time from administration, receptor affinity, behavioral and neurochemical correlates, 5-HT system lesion and circulating glucocorticoid were all relevant factors in determining the rCMRglc effects of 5-HT drugs. Acutely neurotoxic amphetamines markedly increased rCMRglc in brain regions such as the nucleus accumbens that are thought to mediate amphetamine reinforcing properties; on the long term, toxic or electrolytic lesions or chronic treatment with 5-HT agonists produced minimal rCMRglc alterations in spite of marked and persistent changes in 5-HT function. In lesioned or chronically treated rats, acute challanges with 5-HT and non 5-HT agonists demonstrated specific deficits that were not detected in a resting state. Serotonin neuromodulation has been studied in humans by using positron emission tomography with 15O-water. Sequential measurements of regional cerebral blood flow (rCBF) were obtained during combined pharmacological challange with the 5-HT1A agonist buspirone and cognitive activation. Buspirone increased a memory related rCBF activation in task specific regions. This technique can provide a strong theoretical basis for the understanding of 5-HT drug mode of action in normal human brain and in neuropsychiatric diseases. Brain metabolism studies in animals will still be needed to elucidate the factors (e.g. pharmacokinetic and pharmacodynamic) relevant to the cerebral response to 5-HT drugs in humans.
 ...
PMID:Cerebral metabolic effects of serotonin drugs and neurotoxins. 879 99

The effects of delta 9-tetrahydrocannabinol on single-unit activity in the subpostremal division of the nucleus tractus solitarii were investigated by extracellular recording in rat brain slices. The spontaneous firing rate of 54.8% of the recorded neurons was significantly changed after bath applications of delta 9-tetrahydrocannabinol. Putative nutrition-related neurons responding to a moderate increase in glucose concentration were selectively sensitive to delta 9-tetrahydrocannabinol. The delta 9-tetrahydrocannabinol-sensitive neurons were depressed by clonidine and are therefore likely to be adrenergic or noradrenergic. These observations suggest that some catecholaminergic, glucose-responsive neurons in the subpostremal nucleus tractus solitarii might mediate the influence of cannabinoids on feeding behaviour. Furthermore, most delta 9-tetrahydrocannabinol-sensitive neurons in the nucleus tractus solitarii showed opposite responses to delta 9-tetrahydrocannabinol and the 5-HT3 receptor agonist 1-phenylbiguanide, and might therefore be involved in the nausea-reducing effects of cannabinoids.
 ...
PMID:Neuronal responses to delta 9-tetrahydrocannabinol in the solitary tract nucleus. 889 9

The involvement of the peripheral serotonin2A (5-HT2A) receptor in alpha-methyl-5-HT-induced hyperglycemia was examined in rats. The 5-HT2A receptor antagonist, ketanserin, significantly inhibited alpha-methyl-5-HT-elicited hyperglycemia. Taken together with a previous report that 5-HT-induced hyperglycemia was prevented by ketanserin, it is suggested that the peripheral 5-HT2A receptor participates in glucose regulation. As alpha-methyl-5-HT increased serum insulin but did not affect glucagon levels, it is indicated that these pancreatic hormones are probably not related to alpha-methyl-5-HT-induced hyperglycemia. Moreover, the peripheral 5-HT3 receptor agonist, 2-methyl-5-HT, did not affect blood glucose, insulin or glucagon levels. Our results therefore suggest that the peripheral 5-HT3 receptor is not involved in glucose regulation.
 ...
PMID:The effects of peripheral serotonin2 (5-HT2) and serotonin3 (5-HT3) receptor agonists on blood glucose levels in rats. 891 20

The aim of the present study was to investigate the role of central 5-HT3 receptors on the control of blood glucose in stressed and non-stressed rats in both fasted and fed states. Adult Wistar male rats had each their third ventricle cannulated 7 days before the experiments. Injections of m-CPBG, a selective 5-HT3 receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states. The same procedure was unable to modify stress-induced hyperglycemia. The hyperglycemic effect of m-CPBG central administration was blocked by pretreatment with ondansetron, a specific 5-HT3 receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors. Third ventricle injections of ondansetron alone were not able to modify blood glucose in non-stressed animals and did not change the hyperglycemic responses observed after immobilization stress. We conclude that pharmacological activation of the central 5-HT3 receptor induces a hyperglycemic effect in non-stressed animals.
 ...
PMID:Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats. 1197 87

Brain serotonin and CRH systems participate in the control of blood glucose levels. We have previously demonstrated that the pharmacological stimulation of central 5-HT3 receptors, the target for several therapeutic agents used as antiemetics in the course of chemotherapy, induces hyperglycemia. The aim of the present study was to investigate the participation of the brain CRH component and 5-HT3 receptors in basal blood glucose levels as well as in the hyperglycemia induced by third ventricle injections of fluoxetine, a serotonin reuptake inhibitor with a broad range of clinical use. In this study, we used fasted adult Wistar male rats (220 +/- 20 g) whose third ventricles were cannulated 7 days prior to the experiments. Acute third ventricle injections of fluoxetine caused a significant increase in plasma glucose levels throughout the experiment. Pretreatment with alpha-helical CRH, a selective CRH antagonist, significantly blunted fluoxetine-induced hyperglycemia. Also, pretreatment with two distinct selective 5-HT3 receptor antagonists (LY-278,584 and ondansetron) significantly impaired the rise in plasma glucose levels observed in fluoxetine-treated animals pretreated with isotonic saline solution. None of these antagonists was able to modify blood glucose levels when injected alone into the third ventricle. Animals receiving third ventricle injections of fluoxetine, in spite of being hyperglycemic, presented plasma insulin levels similar to those displayed by normoglycemic, saline-treated controls. It is suggested that the acute increase in brain serotonergic activity caused by third ventricle injections of fluoxetine induces a hyperglycemic response that requires the functional integrity of the brain CRH system and 5-HT3 receptors. Also, it is proposed that the absence of a compensatory increase in plasma insulin levels may contribute to the generation of a hyperglycemic response after central fluoxetine administration.
 ...
PMID:Hyperglycemia induced by acute central fluoxetine administration: role of the central CRH system and 5-HT3 receptors. 1522 72

In the present study, we investigated the effect of central serotonergic pathway activation achieved through third ventricle injections of quipazine, a serotonergic agonist, on plasma glucose levels of fasted and fed adult Wistar male rats, whose third ventricles were canulated 7 days before the experiments. Central quipazine administration induced a significant increase in plasma glucose levels in fasted animals, but was unable to modify plasma glucose concentrations in fed rats. Pretreatment with alpha-helical CRH, a CRH antagonist, significantly attenuated quipazine-induced hyperglycemia. Pretreatment with two different 5-HT3 receptor antagonists, LY-278,584 and ondansetron, was also able to produce a significant reduction in the hyperglycemic response evoked by central administration of quipazine. None of the antagonists used was capable of modifying plasma glucose concentrations when injected alone into the third ventricle. Quipazine-treated, hyperglycemic animals did not show any increase in plasma insulin levels. We conclude that acute pharmacological serotonergic stimulation by quipazine produces hyperglycemia by mechanisms that require the functional integrity of both CRH and 5-HT3 receptors, and that impairment in insulin secretion and/or activity may explain hyperglycemia induced by third ventricle injections of quipazine.
 ...
PMID:Hyperglycemia induced by pharmacological activation of central serotonergic pathways depends on the functional integrity of brain CRH system and 5-HT3 receptors. 1613 60

The involvement of 5-hydroxytryptaminergic (5-HTergic) system for the 3-nitropropionic acid (3-NPA)-induced depression of spinal reflexes was evaluated and compared with other energy deficiency condition (ischemia; glucose-free and O2-free). The monosynaptic (MSR) and polysynaptic reflex (PSR) potentials were recorded at ventral root by stimulating the corresponding dorsal root in neonatal rat spinal cord in vitro. Superfusion of 3-NPA (3.4 mM) or ischemic solution depressed the reflexes in a time-dependent manner abolishing them by 35 min. Pretreatment with pindolol (1 microM), ketanserin (10 microM) or ondansetron (0.1 microM); 5-HT1, 5-HT2, or 5-HT3 receptor antagonist, respectively, did not block the 3-NPA-induced depression of reflexes whereas, ischemia-induced depression was blocked by ondansetron. 5-HT content of the spinal cords incubated with 3-NPA (3.4 mM) for 30 min was decreased significantly (33 ng/g tissue) while increased (286 ng/g) in cords exposed to ischemic solution as compared to saline-treated cords (161 ng/g). Thus, 3-NPA-induced depression of spinal reflexes does not involve 5-HTergic pathway unlike ischemia-induced depression.
 ...
PMID:3-Nitropropionic acid-induced depression of spinal reflexes does not involve 5-hydroxytryptaminergic system in contrast to ischemia-induced depression in neonatal rat spinal cord in vitro. 1881 48

Elevated dietary fructose intake, altered intestinal motility, and barrier function may be involved in the development of nonalcoholic fatty liver disease (NAFLD). Because intestinal motility and permeability are also regulated through the bioavailability of serotonin (5-HT), we assessed markers of hepatic injury in serotonin reuptake transporter knockout (SERT(-/-)) and wild-type mice chronically exposed to different monosaccharide solutions (30% glucose or fructose solution) or water for 8 wk. The significant increase in hepatic triglyceride, TNF-alpha, and 4-hydroxynonenal adduct as well as portal endotoxin levels found in fructose-fed mice was associated with a significant decrease of SERT and the tight-junction occludin in the duodenum. Similar effects were not found in mice fed glucose. In contrast, in SERT(-/-) mice fed glucose, portal endotoxin levels, concentration of occludin, and indices of hepatic damage were similar to those found in wild-type and SERT(-/-) mice fed fructose. In fructose-fed mice treated with a 5-HT3 receptor antagonist, hepatic steatosis was significantly attenuated. Our data suggest that a loss of intestinal SERT is a critical factor in fructose-induced impairment of intestinal barrier function and subsequently the development of steatosis.
 ...
PMID:Serotonin reuptake transporter (SERT) plays a critical role in the onset of fructose-induced hepatic steatosis in mice. 1971 74


1 2 Next >>