Disease relevance of Htr3a

• Thus, the profound water secretion that occurs in the early stages of intestinal anaphylaxis is partly 5-HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists [1].
• In the in vivo rat model, 5-HT2a antagonist ketanserin, 5-HT7 agonist 5-carboxamidotryptamine, and (to a limited extent) 5-HT3 antagonist ondansetron could all, like epinastine, block bronchospasm, but the "classic" antihistamine chlorpheniramine was ineffective [2].
• Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog [3].
• These findings strongly suggest that the 5-HT2A receptor subtype, but not the 5-HT3 subtype, is involved in 5-HT-induced hyperalgesia in acute injury and inflammation in the rat [4].
• Agonists acting at 5-HT3 receptors (phenylbiguanide and 2-methyl-5-HT) had no effect on catalepsy [5].

Psychiatry related information on Htr3a

• The interactions of serotonin 5-HT1A, 5-HT1C/2 and 5-HT3 receptor subtypes with apomorphine-induced locomotor activity (AILA) were investigated in Sprague-Dawley rats [6].
• A mechanism of 5-HT3 receptor mediation is involved etiologically in the psychological stress lesion the stomach of the mouse [7].
• The effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on head shaking behavior induced by L-5-HTP and behavioral symptoms induced with 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) in rats was evaluated [8].
• Prevention by the 5-HT3 receptor antagonist, ondansetron, of morphine-dependence and tolerance in the rat [9].
• The role of 5-HT3 receptors in drug dependence [10].

High impact information on Htr3a

• Radioligand binding studies show a high density of 5-HT3 receptors in the cholinergic-rich entorhinal cortex and we provide evidence that a reduction in cortical cholinergic function can be effected in vitro by 5-HT3 receptors [11].
• 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue [11].
• Selective antagonists for the 5-HT3 receptor subtypes which seem to have effects on mood and activity may exert their effect through the regulation of acetylcholine release in the cortex and limbic system [11].
• Recently, GR38032F, MDL 72222 and ICS 205-930 have been shown to have behavioural effects in rodents and primates that undoubtedly reflect an action in the central nervous system (refs 9-11 and unpublished observations), suggesting the existence of 5-HT3 receptors in the brain [12].
• Using these models, selective 5-HT3 receptor antagonists such as MDL 72222 (ref. 5), ICS 205-930 (ref. 6), GR38032F (ref. 7) and BRL 43694 (ref. 8) have been developed [12].

Chemical compound and disease context of Htr3a

• The effects of the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and granisetron, respectively, on water movement during intestinal anaphylaxis were studied [1].
• On the other hand, injection of 5-HT3 receptor agonists (2-methyl 5-HT; 0.86 mg/kg, m-CPG; 8 mg/kg) did not produce hyperalgesia [4].
• Scratching was not affected by ketanserin or by the 5-HT3 receptor antagonist ondansetron, indicating that neither 5-HT2 nor 5-HT3 receptors is involved in itch-associated scratching behavior caused by allergic skin dermatitis in rats [13].
• Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists [8].
• Pretreatment with propranolol (beta-adrenergic receptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2B sites), yohimbine (alpha 2-noradrenergic antagonist that also has binding affinity for 5-HT2B sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate m-CPP-induced hyperthermia [14].

Biological context of Htr3a

• The amino acid sequence predicted from these clones, extending from the putative transmembrane domain I to the stop codon, demonstrated a 93% homology with the 5-HT3 receptor A (R-A) subunit cloned from NCB 20 hybridoma mouse neuroblastoma/Chinese hamster embryonic brain cells [15].
• Therefore, alternative splicing was probably responsible for the presence of short (5-HT3 R-As) and long (5-HT3 R-AL) forms of 5-HT3 R-A mRNA in these ganglia [15].
• Bilateral microinjection of the 5-HT3 receptor agonist, phenylbiguanide (1.7-5 nmol), produced an increase in blood pressure and reduced the cardiovagal component of the baroreflex [16].
• To determine if this pathway plays a role in the pathophysiology of inflammation, we investigated the effects of spinally administered ondansetron (a selective 5HT3 receptor antagonist) on deep dorsal horn neuronal responses in carrageenan inflamed and naïve animals using in vivo electrophysiology [17].
• In 5-HT3A-expressing VIP/CCK interneurons, serotonin induced fast membrane potential depolarizations by activating an inward current that was blocked by the selective 5-HT3R antagonist tropisetron [18].

Anatomical context of Htr3a

• Using in situ hybridization histochemistry, a high degree of coexpression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor was detected in all subfields of the hippocampus and subgranular layer of the dentate gyrus (DG) [19].
• The present experiments on anaesthetized rats investigated the role of 5-HT3 receptors in modulating vagal afferent evoked activity of nucleus tractus solitarius (NTS) neurones [20].
• Semi-quantitative analysis demonstrated that, depending on the hippocampal layer, 72-88% of CB1-expressing interneurons coexpress the 5-HT3A subunit [19].
• PCR was used to isolate identical partial cDNA clones encoding a serotonin 5-HT3 receptor subunit from rat nodose and superior cervical ganglia [15].
• Coexistence of serotonin 3 (5-HT3) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus [19].

Associations of Htr3a with chemical compounds

• These data are consistent with the hypothesis that vagal inputs, including non-myelinated cardiopulmonary inputs to the NTS, utilize a 5-HT-containing pathway which activates 5-HT3 receptors [20].
• However, activation of 5-HT3- or CB1-receptors are likely to have opposing regulatory effects on GABA neurotransmission, as 5-HT3 receptor activation by serotonin results in the release of GABA, while CB1 activation by cannabinoids results in inhibition of GABA release [19].
• This excitatory response to 5-HT3 receptor activation may be partly a direct postsynaptic action but part may also be due to facilitation of the release of glutamate which in turn acts on either non-NMDA or NMDA receptors to evoke excitation [20].
• These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by nonserotonergic mechanisms [21].
• Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats [22].

Physical interactions of Htr3a

• Under such conditions, cortical 5-HT2 receptor binding sites as well as striatal 5-HT3 and dopamine-related binding sites remained unaltered [23].
• Most of the synthesized compounds exhibited moderate-to-very high affinity (in many cases subnanomolar) for the 5-HT4 binding site and no significant affinity for the 5-HT3 receptor [24].

Regulatory relationships of Htr3a

• The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) [18].
• 6. The contractile response to GR43175 in the dog isolated saphenous vein was selectively antagonized by methiothepin but was resistant to antagonism by the 5-HT2 receptor blocking drug ketanserin and the 5-HT3 receptor blocking drug MDL 72222 [25].
• Gastric distension enhances CCK-induced Fos-like immunoreactivity in the dorsal hindbrain by activating 5-HT3 receptors [26].
• These data suggest that 5-HT4 receptor activation enhances the ability of 5-HT3 receptor activation to induce intestinal allodynia [27].
• These results suggest that 5-HT3 receptor activation may be required for amphetamine-induced expression of ATF-1-regulated target genes in the striatum, which may include c-Fos [28].

Other interactions of Htr3a

• Conversely, neither 5-HT1, 5-HT2 nor 5-HT3 receptors played a role in the hyperglycaemic response to 2-DG [29].
• Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum [30].
• In anaesthetized rats, the 5-HT1A antagonist, spiroxatrine (1 mg/kg), and the 5-HT3 receptor antagonist, MDL72222 (0.3 mg/kg), selectively diminished the hypotensive phase without affecting the pressor phase [31].
• Double-labeled 5-HT3A/CB1 neurons were found in the anterior olfactory nucleus, superficial and deep layers of the cortex, hippocampal formation (hippocampus, dentate gyrus, subiculum, and entorhinal cortex) and amygdala [32].
• 5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons [18].

Analytical, diagnostic and therapeutic context of Htr3a

• PCR experiments, with specific primers located upstream and downstream of the GSLLP deletion, were used to detect reverse transcribed 5-HT3 R-A mRNAs [15].
• We report the nucleotide and deduced amino acid sequences of a nearly complete rat 5-HT3 receptor subunit and use the sequence to develop a reverse transcription-polymerase chain reaction (RT-PCR) assay that measures 5-HT3 mRNA [33].
• In this study, we report the presence and distribution of 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum using immunofluorescence histochemistry [30].
• Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT1A, 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models [34].
• Finally, central 5-HT1 and/or 5-HT2, but not 5-HT3, receptors may underlie the suppressant effects of dexfenfluramine on heroin self-administration [35].

References