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)

1. 5-Hydroxytryptamine (5-HT) has been shown to induce contraction of tracheal smooth muscle. However, the mechanisms of action of 5-HT are not known. We therefore investigated the effects of 5-HT on phospholipase C (PLC)-mediated phosphoinositide (PI) hydrolysis and its regulation in canine cultured tracheal smooth muscle cells (TSMCs) labelled with [3H]-inositol. 5-HT-induced inositol phosphates (IPs) accumulation was time- and dose-dependent with a half-maximal response (EC50) and a maximal response at 0.38 +/- 0.05 and 10 microM, respectively. 2. Ketanserin and mianserin (10 and 100 nM), 5-HT2 receptor antagonists, were equipotent in blocking the 5-HT-induced IPs accumulation with pKB values of 8.46 and 8.21, respectively. In contrast, the dose-response curves of 5-HT-induced IPs accumulation were not shifted until the concentrations of NAN-190 and metoclopramide (5-HT1A and 5-HT3 receptor antagonists, respectively) were increased up to 10 microM. 3. Pretreatment of TSMCs with pertussis toxin or cholera toxin did not inhibit the 5-HT-induced IPs accumulation, but partially inhibited the AlF(4-)-induced IPs response. 4. Stimulation of IPs accumulation by 5-HT required the presence of external Ca2+ and was blocked by EGTA. The addition of Ca2+ (3-620 nM) to digitonin-permeabilized TSMCs directly stimulated IPs accumulation. A further Ca(2+)-dependent increase in IPs accumulation was obtained by inclusion of either guanosine 5'-O-(3-thiotriphoshate) (GTP gamma S) or 5-HT. The combination of GTP gamma S and 5-HT elicited an additive effect on IPs accumulation. 5. Treatment with phorbol 12-myristate 13-acetate (PMA, 1 microM, 30 min) abolished the 5-HT-induced IPs accumulation. The concentrations of PMA that gave a half-maximal and maximal inhibition of 5-HT-induced IPs accumulation were 2.2 +/- 0.4 nM and 1 microM, n = 3, respectively. The protein kinase C (PKC) activator, 4 alpha-phorbol 12,13-didecanoate, at 1 microM, did not influence this response. The inhibitory effect of PMA was reversed by staurosporine, a PKC inhibitor, suggesting that the inhibitory effect of PMA is mediated through the activation of PKC. 6. The site of this inhibition was further investigated by examining the effect of PMA on AlF(4-)-induced IPs accumulation in canine TSMCs. AlF(4-)-stimulated IPs accumulation was inhibited by PMA treatment, suggesting that the effect of PMA is distal to the 5-HT receptor. 7. Acetylcholine-induced IPs accumulation was completely inhibited by atropine, but not affected by ketanserin or mianserin, suggesting that 5-HT-induced IPs accumulation is not due to release of acetylcholine.8. These results demonstrate that 5-HT directly stimulates PLC-mediated PI hydrolysis via a pertussis toxin- and cholera toxin-insensitive GTP binding protein in canine TSMCs and that this coupling process is negatively regulated by PKC. 5-HT2 receptors may be predominantly mediating IPs accumulation and presumably IP-induced Ca2+ release may function as the transducing mechanism for 5-HT stimulated contraction of tracheal smooth muscle.
 ...
PMID:5-Hydroxytryptamine receptor-mediated phosphoinositide hydrolysis in canine cultured tracheal smooth muscle cells. 801 56

Functional interactions between serotonergic (5-HT) and opioid drugs have been observed with 5-HT3 receptor antagonism enhancing the inhibitory actions of naloxone and naltrexone in both food-deprived and glucoprivic rats; 5-HT2A/C receptor antagonism enhanced naltrexone's inhibition of insulin hyperphagia. The present study examined whether pretreatment with either general 5-HT (methysergide: 0.5-5 mg/kg), 5-HT2A/C (ritanserin: 0.25-2.5 mg/kg), or 5-HT3 (ICS 205930: 0.5-5 mg/kg) antagonists altered the pattern and magnitude of ad lib intake of simple (sucrose: 10%) or more complex (maltose dextrin: MD, 10%) carbohydrate solutions, or naltrexone's (0.25-2.5 mg/kg) inhibition of these forms of intake. Methysergide significantly increased the pattern and magnitude of sucrose intake at low (0.5-2.5 mg/kg) doses, and transiently delayed the pattern of MD intake at high (5 mg/kg) doses. Ritanserin significantly accelerated the pattern, but not the magnitude of sucrose intake at low (0.25-1.25 mg/kg) doses without affecting MD intake. ICS 205930 reduced the magnitude of sucrose intake at the highest (5 mg/kg) dose, and transiently reduced MD intake. Naltrexone dose dependently altered the pattern and magnitude of both sucrose and MD intake. Coadministration of ritanserin and naltrexone either eliminated or delayed the pattern of opioid antagonist inhibition of both sucrose and MD intake. Methysergide and ICS 205930 pretreatment produced minor changes in the pattern of naltrexone-induced inhibition. These data indicate that 5-HT receptor differentially modulate the pattern of carbohydrate intake, and indicate differential ingestive interactions between 5-HT and opioid antagonists under challenge and palatable conditions.
 ...
PMID:Naltrexone, serotonin receptor subtype antagonists, and carbohydrate intake in rats. 802 91

The ability of 5-HT receptor agonists to modulate the electrically evoked release of [3H]noradrenaline was tested on preloaded slices of the rat brain. The 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) (10-100 microM) concentration-dependently enhanced the electrically evoked release of [3H]noradrenaline in the hippocampus and the hypothalamus, but only at 100 microM in the frontal cortex. The enhancing effect of 2-methyl-5-HT was blocked by the 5-HT3 receptor antagonist ondansetron. Elevated levels of endogenous 5-HT, achieved through selective reuptake blockade with paroxetine, as well as the addition of exogenous 5-HT in the medium, also enhanced [3H]noradrenaline release. Furthermore, this effect of paroxetine was blocked by nanomolar concentrations of the 5-HT3 receptor antagonists ondansetron, tropisetron and (S)-zacopride. Only high concentrations of the 5-HT3 receptor agonist m-chlorophenylbiguanide increased [3H]noradrenaline release from hippocampal slices, and this effect was not blocked by ondansetron nor by (S)-zacopride. The possibility that the enhancing effect of 2-methyl-5-HT could have been due to the antagonism of alpha 2-autoreceptors of noradrenergic terminals was ruled out by the unaltered effectiveness of the alpha 2-adrenoceptor agonist UK-14,304 (1 microM) to attenuate [3H]noradrenaline release in the presence of 100 microM of 2-methyl-5-HT. Moreover, in pseudo-one-pulse experiments 100 microM of 2-methyl-5-HT increased [3H]noradrenaline release in the absence of autoinhibition through alpha 2-adrenergic autoreceptors. The 5-HT1A and 5-HT1B receptor agonists 8-hydroxy-2(di-n-propyl-amino)tetralin and CP-93,129, respectively, as well as the 5-HT1 receptor agonist 5-carboxyamidotryptamine, were devoid of effect on the release of [3H]noradrenaline. The 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane increased the release of [3H]noradrenaline, but this effect was not blocked with the 5-HT3 receptor antagonist ondansetron. Lesioning 5-HT fibers with the neurotoxin 5,7-dihydroxytryptamine did not alter the action of 2-methyl-5-HT on [3H]noradrenaline release, indicating that this effect is not attributable to an action of this 5-HT3 receptor agonist on 5-HT terminals.
 ...
PMID:Activation of 5-HT3 receptors enhances the electrically evoked release of [3H]noradrenaline in rat brain limbic structures. 804 71

Rats were trained to discriminate the 5-HT receptor agonist m-chlorophenylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-reinforced drug discrimination task. The antidepressant trazodone (1-8 mg/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully for mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 receptor or the 5-HT reuptake site produced saline-lever responding. The ergoline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist/antagonist profile. The 5-HT1/2 receptor antagonist metergoline (0.125-1 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C receptor antagonists ketanserin and LY 53857 as well as all other 5-HT receptor antagonists failed to block the mCPP cue. The dopamine receptor antagonists SCH 23390 and haloperidol were also ineffective mCPP antagonists. Following pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the discriminability of low doses of mCPP increased, whereas the effects of fenfluramine decreased. The present results suggest that the discriminative stimulus effects of mCPP in rats are mediated primarily by postsynaptic 5-HT2C receptors.
 ...
PMID:Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). 808 4

The purpose of the present study was to investigate the effect of microinjection of serotonin (5-HT) and selected 5-HT receptor subtype agonists and antagonists into the caudal nucleus raphe obscurus on gastrointestinal motor activity in urethane-chloralose anesthetized rats. Serotonin (0.6-18.0 nmol) dose-dependently increased intragastric pressure, and this effect was abolished by peripherally administered atropine (0.5-1.0 mg/kg, i.v.). Microinjection of a 5-HT1A receptor agonist, 8-hydroxy-N,N-dipropyl-2-amino-tetralin hydrobromide (0.06-12.0 nmol), a 5-HT1C/2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (4.5 and 18.0 nmol), as well as a 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (0.6-18.0 nmol), also resulted in increases in intragastric pressure. The gastric excitatory effect of 5-HT (6.0 nmol) was markedly reduced by prior microinjection of a 5-HT1/2 receptor antagonist, methiothepin (200 nmol), into the same site, as well as by i.v. administration of a 5-HT2/1C antagonist, ketanserin (2.5 mg/kg). The effect of 5-HT (6.0 nmol) on intragastric pressure was completely blocked by i.v. administration of a mixture of the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazinehydrobromide++ + (3.5 mg/kg), ketanserin (2.5 mg/kg) and the 5-HT3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (2.5 mg/kg). These results indicate that 5-HT activates gastric motor function in the caudal nucleus raphe obscurus via a vagally mediated pathway and that the activation of multiple 5-HT receptor subtypes is required for the gastric excitatory effect of 5-HT.
 ...
PMID:Serotonin microinjected into the nucleus raphe obscurus increases intragastric pressure in the rat via a vagally mediated pathway. 809 47

To characterize the 5-hydroxytryptamine (5-HT) receptors, the contractile effects of both 5-HT and the 5-HT1-like receptor agonist sumatriptan were investigated in isolated open ring preparations of the rabbit common iliac artery. 5-HT induced concentration-dependent contractions. Sumatriptan did not induce any contraction of unstimulated preparations, whereas it elicited concentration-dependent contractions in preparations given a moderate tone with a threshold concentration of prostaglandin F2 alpha. In vessel segments precontracted with prostaglandin F2 alpha, Emax values for 5-HT and sumatriptan reached about 85% and 30% of the phenylephrine maximal effect, respectively. The mean EC50 values for sumatriptan and 5-HT were 3.34 microM and 1.5 microM, respectively. Pargyline, cocaine or normetanephrine were without significant effect on the contractions induced by 5-HT or sumatriptan. The 5-HT3 receptor antagonist tropisetron (1 microM) had no effect on 5-HT- and sumatriptan-induced contractions. The 5-HT2 receptor antagonist ketanserin (0.1-1 microM) produced parallel displacements to the right of the 5-HT and phenylephrine concentration-effect curves, without significant reduction in the maximum responses. The pA2 values were 7.85 +/- 0.19 and 7.9 +/- 0.16, respectively. Ketanserin had no effect on the sumatriptan concentration-effect curves. The nonselective 5-HT receptor antagonists methysergide (0.3 microM) and methiothepin (0.01 microM) shifted the concentration-response curve to sumatriptan to the right (mean pKB values of 6.91 and 8.68, respectively). The pA2 value for prazosin against 5-HT (9.98 +/- 0.43) was not significantly different from the value against phenylephrine (9.27 +/- 0.20). These results suggest that the sumatriptan-induced contraction is mediated by a 5-HT1-like receptor, whereas an additional mechanism, probably an alpha 1-adrenoceptor stimulation, plays a role in the contraction induced by 5-HT in the rabbit iliac artery.
 ...
PMID:Characterization of 5-hydroxytryptamine receptors in rabbit isolated iliac artery. 818 15

Dumuis and colleagues (1988) in their investigation of a 5-HT receptor positively linked to adenylate cyclase in the central nervous system, concluded that the receptor was not 5-HT1, 5-HT2 or 5-HT3-like and suggested that it belonged to a new class of 5-HT receptor called 5-HT4. A similar, if not identical receptor was located by Craig and Clark (1990) in the guinea pig ileum and a functional role for the peripheral 5-HT4 receptor has since been established in many species to mediate muscle contraction or relaxation within the gut and positive inotropic effects in the heart. In contrast, a functional role for central 5-HT4 receptors has remained obscure. Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH-DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation. 5-Hydroxytryptophan has the opposite effect exacerbating the behavioural response to the aversive situation. But an anxiolytic profile is revealed by co-treatment with ritanserin plus 5-hydroxytryptophan. The drug-induced anxiolytic profiles are inhibited by SDZ205-557 and a high dose of tropisetron. Both compounds are 5-HT3/5-HT4 receptor antagonists yet the selective 5-HT3 receptor antagonist ondansetron fails to inhibit the drug-induced anxiolytic profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The pharmacology of the 5-HT4 receptor. 820 Dec 42

The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine and the 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were examined in a dietary paradigm that appears to be sensitive to 5-HT-induced carbohydrate suppression. In this paradigm, deprived rats are provided with a nutritionally complete hydrated chow mash diet together with an optional carbohydrate supplement of powdered Polycose. Both d-fenfluramine and DOI produced a clear suppression of total energy intake and carbohydrate (Polycose) intake. However, the mechanisms underlying these effects are different. The effect of d-fenfluramine in this paradigm was attenuated by the 5-HT1/5-HT2 receptor antagonist metergoline and partially attenuated by the 5-HT1A/5-HT1B receptor antagonist (+/-)cyanopindolol. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS-205,930), the 5-HT2/5-HT1C receptor antagonist ritanserin, or the peripheral 5-HT receptor antagonist xylamidine. However, the effect of DOI in this paradigm was significantly attenuated by ketanserin but was not antagonised by either ritanserin or (+/-)cyanopindolol. Therefore, the suppressive effect of these two 5-HT drugs on total and Polycose intake appears to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5-HT2 receptors (DOI).
 ...
PMID:5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d-fenfluramine and DOI. 826 89

Typical neuroleptics (e.g. haloperidol) can induce catalepsy in rodents. Selective 5-hydroxytryptamine1A (5-HT1A) receptor antagonists reduce neuroleptic-induced catalepsy (NIC), suggesting that this subtype of serotonin receptor plays a role in the modulation of nigrostriatal dopaminergic transmission. The present study was designed to evaluate the participation of other 5-HT receptor subtypes in NIC. Adult albino mice (both sexes, 26-35 g) were used. Catalepsy was induced with haloperidol (H; 1.5 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Cyanopindolol (a 5-HT1B receptor antagonist), ICI 169,369 (a 5-HT1C/2 receptor antagonist) and granisetron (a 5-HT3 receptor antagonist) were used. Buspirone, a 5-HT1A partial antagonist, cisapride, a 5-HT3/5-HT4 ligand and clomipramine, a 5-HT neuronal uptake blocker, were also employed. These drugs were injected ip, 20 min before H, with each animal (9-10 per group) used only once. Cyanopindolol (0.3 mg/kg) or ICI 169,369 (5 mg/kg) did not significantly affect NIC (375 +/- 39 and 378 +/- 34 s vs 372 +/- 44 s for controls, at 2 h after H). Buspirone (1 mg/kg) reduced, while pretreatments with either granisetron (0.5 mg/kg), cisapride (5 mg/kg) or clomipramine (5 mg/kg) potentiated the cataleptic effect of H (107 +/- 19, 576 +/- 52, 815 +/- 76 and 800 +/- 97 s vs 374 +/- 40 s in the control group, at 2 h after H).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of the 5-HT receptor antagonists cyanopindolol, ICI 169,369, cisapride and granisetron on neuroleptic-induced catalepsy in mice. 829 21

C57BL/6 mice exhibit acute transient decreases in lung conductance (GL) and dynamic compliance (Cdyn) after intravenous administration of serotonin (5-HT). To identify the specific agonist receptor subtypes responsible for this bronchoconstriction, we measured changes in pulmonary function in C57BL/6 mice in response to intravenous infusion of 5-HT receptor subtype-selective agonists and to 5-HT in the presence of antagonists selective for the 5-HT2 or 5-HT3 receptor subtypes. Agonists selective for the 5-HT1A/1B/1D or 5-HT3 receptor subtypes induced minimal or undetectable pulmonary responses, whereas infusion of alpha-methyl-5-hydroxytryptamine, a 5-HT2 receptor-selective agonist, led to dose-related decreases in Cdyn and GL. The selective 5-HT3 receptor antagonist, LY278584 maleate, (1.0 mg/kg i.v.) caused no detectable reduction in the response to 100 micrograms/kg of 5-HT. In contrast, treatment with the 5-HT2 receptor antagonist LY53857 (10 micrograms/kg i.v.) resulted in a significant diminution of the pulmonary response observed after infusion of 100 micrograms/kg of 5-HT. Dose-response relationships were established for 5-HT in experiments in which each mouse was treated with a single dose of 5-HT without antagonist or after LY53857. Compared with responses to doses of 5-HT of more than 100 micrograms/kg in the absence of antagonist, pulmonary responses to 5-HT after infusion of 10 micrograms/kg of LY53857 were significantly reduced; 100 micrograms/kg of LY53857 nearly abolished the responses to all doses of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonin-induced pulmonary responses are mediated by the 5-HT2 receptor in the mouse. 830 45


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>