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)

Radiation inactivation was used to determine the molecular target size of the binding site for [3H]GR65630, a specific 5-HT3 receptor ligand, in two different neuronal tissues. Using a calibration curve of known molecular weight enzymes, the target sizes of [3H]GR65630 binding sites in N1E-115 neuroblastoma cells and rat brain were 98,600 +/- 11,300 and 49,100 +/- 8,500 Da, respectively. The results suggest 5-HT3 receptors may be present as dimers in N1E-115 neuroblastoma cells.
Eur J Pharmacol 1990 Sep 18
PMID:Target size of 5-HT3 receptors in N1E-115 neuroblastoma cells and rat brain. 225 5

The effect of ketanserin (3 mg/kg i.v.) on the baroreceptor heart rate reflex and the Bezold-Jarisch reflex was examined in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the control situation (before ketanserin treatment), reflex bradycardia in response to phenylephrine (baroreflex) and phenyldiguanide (Bezold-Jarisch reflex) were impaired in SHR as compared with WKY, while reflex tachycardia in response to nitroprusside was similar in the two groups. However, after ketanserin administration in SHR, there was a reversal of the baroreflex-mediated tachycardia in response to nitroprusside into a bradycardic response. The nitroprusside-induced bradycardia was not caused by the release of 5-HT stimulating chemosensitive vagal afferents since the 5-HT3 receptor antagonist MDL 72222 did not block this response. In the same SHR, the Bezold-Jarisch reflex evoked by phenyldiguanide and the phenylephrine-induced bradycardia were potentiated by ketanserin. All the above effects of ketanserin were less evident in the WKY. Ketanserin did not alter vagal efferent function in anaesthetized SHR since it did not affect bradycardia induced by electrical stimulation of the vagus nerve. Therefore, it is suggested that ketanserin has sensitised cardiac vagal afferent mechanisms in SHR, which led to a normalization of reflex bradycardic function to a level normally observed in conscious normotensive WKY (i.e. prior to ketanserin treatment).
Eur J Pharmacol 1990 Sep 04
PMID:The effect of ketanserin on cardiovascular reflexes in conscious normotensive and spontaneously hypertensive rats. 228 35

The 5-HT3 receptor antagonists ICS 205-930 and zacopride attenuated cocaine-induced locomotor activity in C57BL/6ByJ mice. In contrast, the aselective 5-HT1 and 5-HT2 receptor antagonist, methysergide did not affect the response to cocaine. The effect of the 5-HT3 receptor antagonists was not due to general sedation, because zacopride did not alter the locomotor response to caffeine.
Eur J Pharmacol 1990 Sep 21
PMID:5-HT3 receptor antagonists attenuate cocaine-induced locomotion in mice. 228 34

DOI (1-100 micrograms/kg i.v.) induced an increase in mean blood pressure in the anaesthetized rat. Similarly, in the pithed rat, DOI (1-100 micrograms/kg i.v.) induced a dose-dependent increase in mean blood pressure, as did 5-HT. However, in contrast to 5-HT, DOI did not change the heart rate in either intact or pithed rats. In the pithed rat, the dose-pressor response curves to both 5-HT and DOI were unaffected by MDL 72222 (5-HT3 receptor antagonist), spiroxatrine or (+/-)-pindolol (5-HT1A receptor antagonists), idazoxan (alpha 2-adrenoceptor blocking agent) and AR-C 239 (alpha 1-adrenoceptor blocking agent). Only the selective 5-HT2 receptor antagonist. LY 53857, significantly and dose dependently shifted to the right the dose-response curves to both 5-HT and DOI. These results indicated that DOI possesses 5-HT2 agonistic properties and that the pressor response induced by DOI in the pithed rat is mediated via 5-HT2 receptors.
Eur J Pharmacol 1989 Sep 22
PMID:Characterization of DOI, a putative 5-HT2 receptor agonist in the rat. 258 42

Serotonin (5-HT) induces a large inward current accompanied by a conductance increase when applied focally to either neurons of mouse hippocampal cultures or cells of the NG108-15 clonal cell line. In both systems, the response is blocked by ICS 205-930, curare, and metoclopramide, while 2-methyl-5-HT is an agonist. The actions of ICS 205-930 and 2-methyl-5-HT indicate that the response is mediated by the 5-HT3 receptor. In NG108-15 cells the response activated in as little as 35 ms. The rapidity of the response suggests a direct coupling between the 5-HT3 receptor and a channel, which are probably both part of a single membrane protein. In both cell types, prolonged application of 5-HT resulted in desensitization; the rates of desensitization were accelerated by the adenylate cyclase activator forskolin. The 5-HT3 receptor has much in common with the nicotinic receptor and is probably involved in rapid synaptic transmission in the mammalian brain. Since this response is modulated by manipulations that elevate intracellular cAMP levels, the central synapses in which this receptor operates may exhibit plasticity.
Neuron 1988 Sep
PMID:5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. 327 81

Recent studies have implicated 5-HT3(5-HT-M) receptors in the genesis of retching and vomiting evoked by antineoplastic agents. Such receptors have so far only been located peripherally, notably on the vagus. Therefore, the effects of bilateral abdominal vagotomy and antagonism of 5-HT3 receptors have been investigated on retching and vomiting induced by radiation. The gastrokinetic substituted benzamide BRL24924, (Beecham Pharmaceuticals) which has 5-HT3 receptor antagonist properties, was used. Using the ferret, it was shown that whole body x-radiation produced retching and vomiting, which was most severe during the 30 min following irradiation, and continued for at least 90 min. Abdominal vagotomy almost totally abolished the retching and vomiting, occurring during the 30 min immediately after irradiation. The following 60 min period was similar to that of control animals. This would suggest that the emetic events can be divided into a vagally-dependent and independent phase. In a small dose, BRL 24924 mimicked abdominal vagtotomy, in a larger dose, it almost totally abolished the retching and vomiting throughout the entire 90 min period. These results suggest that 5-HT3 receptor antagonists are capable of ameliorating radiation-induced retching and vomiting and that, while an important site of their action could be the abdominal vagi, other areas are probably also involved.
Neuropharmacology 1987 Sep
PMID:Evidence for an extra-abdominal site of action for the 5-HT3 receptor antagonist BRL24924 in the inhibition of radiation-evoked emesis in the ferret. 367 May 59

The serotonin (5HT3) antagonist ondansetron was compared in a randomised study with metoclopramide and dexamethasone for the prevention of chemotherapy induced emesis. Thirty children aged 1-15 years with acute lymphoblastic leukaemia received 'intensification modules' according to the MRC United Kingdom acute lymphoblastic leukaemia regimen UKALL XI. This contains the moderately emetogenic drugs daunorubicin, etoposide, and cytarabine. Fifteen children received an intravenous loading dose of ondansetron followed by intravenous or oral doses 12 hourly for five days. Fifteen children received intravenous metoclopramide every six hours for three days with a loading dose of dexamethasone, repeated every eight hours for three days intravenously or orally. Efficacy was assessed by a diary card documenting the incidence of nausea, retching, or vomiting. In the 24 hour period after starting chemotherapy, ondansetron was more effective, with a complete or major response rate of 93%, compared with 33% using metoclopramide/dexamethasone.
Arch Dis Child 1995 Sep
PMID:Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis. 749 64

We used conventional intracellular recording methods to examine the effects of YM060 [(-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole monohydrochloride), a novel 5-HT3 receptor antagonist, on 5-hydroxytryptamine (5-HT, serotonin)-evoked fast membrane depolarization in myenteric neurons of the guinea pig distal colon, and compared its potency to that of other 5-HT3 receptor antagonists. Microapplication of 5-HT from fine-tipped pipettes evoked both fast and slowly activating depolarizing responses in 78% and 40% of colonic myenteric neurons, respectively. The selective 5-HT3 receptor agonist 2-methyl-5-HT applied with short pressure pulses (100-300 ms) mimicked the fast but not the slow response. The 5-HT3 receptor antagonists YM060, granisetron and ondansetron suppressed the 5-HT-evoked fast response in 98% of colonic myenteric neurons in a concentration-dependent manner with pIC50 values of 8.62, 7.77 and 6.90, respectively. Methysergide and GR113808 did not affect the fast responses at concentrations sufficient to block 5-HT1, 5-HT2 and 5-HT4 receptors, respectively. YM060 did not affect the slowly activating response to 5-HT or any other electrophysiological parameter of the neurons including resting membrane potential, input resistance and the amplitude of action potentials evoked by injection of depolarizing current. Stimulus-evoked fast excitatory postsynaptic potentials were unchanged by YM060 at concentrations up to 10(-8) M, excluding any possible local anesthetic or anticholinergic effects of YM060. The results confirm that the fast component of the two depolarizing responses to 5-HT in colonic myenteric neurons is mediated by 5-HT3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Eur J Pharmacol 1995 Sep 05
PMID:Inhibitory effect of YM060 on 5-HT3 receptor-mediated depolarization in colonic myenteric neurons of the guinea pig. 749 99

Loading therapy consisting of the ACNU regimen was instituted as postoperative anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy. The former could be prevented by the administration of G-CSF, but platelet infusions were necessary in some patients for amelioration of thrombocytopenia. Gastroenterological symptoms, such as nausea and vomiting, were also frequently noted. Granisetron (Kytril), which is a recently developed selective competitive inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse effects, and was found to be clinically effective.
Gan To Kagaku Ryoho 1994 Sep
PMID:[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs]. 752 1

Effects of Pb and several other metal ions on various distinct types of voltage-, receptor- and Ca-activated ion channels have been investigated in cultured N1E-115 mouse neuroblastoma cells. Experiments were performed using the whole-cell voltage clamp and single-channel patch clamp techniques. External superfusion of nanomolar to submillimolar concentrations of Pb causes multiple effects on ion channels. Barium current through voltage-activated Ca channels is blocked by micromolar concentrations of Pb, whereas voltage-activated Na current appears insensitive. Neuronal type nicotinic acetylcholine receptor-activated ion current is blocked by nanomolar concentrations of Pb and this block is reversed at micromolar concentrations. Serotonin 5-HT3 receptor-activated ion current is much less sensitive to Pb. In addition, external superfusion with micromolar concentrations of Pb as well as of Cd and aluminum induces inward current, associated with the direct activation of nonselective cation channels by these metal ions. In excised inside-out membrane patches of neuroblastoma cells, micromolar concentrations of Ca activate small (SK) and big (BK) Ca-activated K channels. Internally applied Pb activates SK and BK channels more potently than Ca, whereas Cd is approximately equipotent to Pb with respect to SK channel activation, but fails to activate BK channels. The results show that metal ions cause distinct, selective effects on the various types of ion channels and that metal ion interaction sites of ion channels may be highly selective for particular metal ions.
Environ Health Perspect 1994 Sep
PMID:Metal interactions with voltage- and receptor-activated ion channels. 753 Nov 39


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