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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.
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PMID:Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro. 139 88

1. Neuronal 5-hydroxytryptamine (5-HT) receptors mediating contraction of guinea-pig ileal segments have been characterized in vitro by the use of methysergide to block 5-HT1-like and 5-HT2 receptors. Concentration-response curves to 5-HT were biphasic (first phase, defined as those responses occurring between 1 nM and 0.32 microM 5-HT, -log EC50 = 7.15 +/- 0.08; second phase, defined as these responses occurring between 0.32 microM and 32 microM 5-HT, -log EC50 = 5.32 +/- 0.03) but monophasic to 5-methoxytryptamine (-log EC50 = 7.0 +/- 0.08) and 2 methyl 5-HT (-log EC50 = 5.2 +/- 0.13). The maximal response of the first phase to 5-HT and the maximal response to 5-methoxytryptamine were 30 +/- 4% and 35 +/- 5% respectively of the maximum response to the second phase of the 5-HT concentration-effect curve (set at 100%). In contrast, the maximal response to 2-methyl-5-HT equalled that obtained with 5-HT (second phase). 2. The responses comprising the second phase of the concentration-effect curve to 5-HT were antagonized by 1 microM ICS 205-930, ondansetron, granisetron, quipazine, N-methyl-quipazine and (R,S)-zacopride and the following pKB values, with 5-HT as the agonist, were obtained at the 5-HT3 receptor: ICS 205-930 7.61 +/- 0.05, ondansetron 6.90 +/- 0.04, granisetron 7.90 +/- 0.04, (S)-zacopride 8.11 +/- 0.06, (R,S)-zacopride 7.64 +/- 0.11, and (R)-zacopride 7.27 +/- 0.06. 3. Under conditions of 5-HT1-like, 5-HT2 and 5-HT3 receptor blockade, the following rank order of agonism was observed: 5-HT > 5-methoxytryptamine = renzapride > (S)-zacopride > (R,S-zacopride > 5-carboxamidotryptamine > BRL 24682 > (R-zacopride > metoclopramide > 2-methyl-5-HT > sulpiride. 8-Dihydroxydiphenylaminotetralin (8-OHDPAT), GR 43175, N,N-dipropyl-5-carboxamidotryptamine, ondansetron, ICS 205-930, granisetron, quipazine and N-methyl-quipazine were inactive as agonists and antagonists. Relative to 5-HT, (R,S)-zacopride acted as a partial agonist (intrinsic activity, alpha = 0.80; -log EC50 = 6.3 + 0.12; -log KA = 6.1 + 0.03) as did (R)-zacopride (alpha = 0.4, -log EC,0 5.7 + 0.08, -log KA = 5.5 + 0.11). (S)-zacopride acted as a full agonist (-log EC,0 = 6.9 + 0.03). ICS 205-930 (3 microM) antagonized competitively responses to 5-HT, 5 methoxytryptamine, (RS)- and (S)- zacopride and 5-carboxamidotryptamine yielding -log KB estimates ranging from 6.1-6.5. 4. It is concluded that two different 5-HT receptors mediate excitatory neuronal responses in the guineapig ileum. 5-HT3 receptors mediate the second phase of the biphasic concentration-response curve, whereas a receptor with properties distinct from the 5-HT1-like, 5-HT2 and 5-HT3 subtypes mediates the initial phase of the concentration-response curve. This receptor, which exhibits a close similarity to the 5-HT4 subtype is: (1) stimulated by 5-methoxytryptamine but not 2-methyl-5-HT; (2) stimulated selectively by certain substituted benzamides; (3) recognizes the optical isomers of zacopride and (4) is blocked by relatively high concentrations ICS 205-930 (pKB = 6.0-6.5) but not ondansetron, granisetron, quipazine or N-methyl-quipazine.
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PMID:Characterization of 5-HT3 and 'atypical' 5-HT receptors mediating guinea-pig ileal contractions in vitro. 207 74

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.
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PMID:Serotonin microinjected into the nucleus raphe obscurus increases intragastric pressure in the rat via a vagally mediated pathway. 809 47

The 5-HT (5-hydroxytryptamine)-induced contractile biphasic concentration-effect curve in rat isolated jejunum was investigated. The pEC50 values for the first and second phases were 8.0 and 6.1, respectively. The responses were insensitive to atropine (0.1 microM), ketanserin (2 microM), (-)-pindolol (5 microM), yohimbine (0.1 microM) and GR 113808 ({1-[2-(methyl-sulphonylamino)ethyl]-4-piperidinyl}methyl 1-methyl-1 H-indole-3-carboxylate, 1 microM) but susceptible to cocaine (10 microM). The low affinity phase was blocked by tetrodotoxin (1 microM), ondansetron (1 microM) and SR48968 (S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide, 0.1 microM). The high affinity phase was antagonised non-surmountably by fluoxetine (1 microM) methysergide (0.1 microM), spiperone (0.1 microM) and methiothepin (0.1 microM). Ritanserin (0.01-0.1 microM) and mesulergine (0.01-0.1 microM) acted as surmountable, competitive antagonists with pA2 values of 8.0 and 8.1, respectively. Clozapine (0.1 microM) was a surmountable antagonist with an apparent pA2 value of 8.0. The rank potency order of the 5-HT receptor agonists was 5-CT (5-carboxyamidotryptamine) > or = 5-HT = 5-methoxytryptamine > or = alpha-methyl-5-HT > > 8-OH-DPAT ((+/-)-2-dipropyl-amino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene) > dipropyl-5-CT > renzapride = sumatriptan. The responses to 5-HT and 5-CT were not potentiated by pargyline (10 and 100 microM). It is suggested that rat jejunum contains a neuronal 5-HT3 receptor facilitating neurokinin release and a contractile smooth muscle 5-HT receptor with a pharmacological operational profile similar to the cloned 5-ht7 receptor.
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PMID:Characterisation of a postjunctional 5-ht7-like and a prejunctional 5-HT3 receptor mediating contraction of rat isolated jejunum. 889 99

1. In isolated human placental chorionic vein segments, 5-hydroxytryptamine (5-HT; 10(-8) to 5 x 10(-5) M) elicited concentration-dependent contractions with EC50 = 5.5 (5.2-5.7) x 10(-8) M) and Emax = 93.1 +/- 7.3% of 75 mM KCl-induced contraction. 2. The agonist of 5-HT2 receptors, alpha-methyl-5-hydroxytryptamine, and the selective agonist of 5-HT1 receptors, N,N-dipropyl-5-carboxamidotryptamine and 5-carboxamidotryptamine, induced pronounced concentration-related contractions, which reached 71.1 +/- 6.0%, 53.0 +/- 5.0% and 75.0 +/- 7.8% at the highest dose tested, respectively. The agonist of 5-HT3 receptor, 2-methyl-5-hydroxytryptamine, reached a maximum averaging 36.7 +/- 5.1% of the maximal response to KCl. 3. The 5-HT1 and 5-HT3 receptor antagonists, methiothepin and metoclopramide (10(-7) to 10(-6) M) did not alter the response to 5-HT. However, ketanserin (10(-7) to 10(-6) M), a 5-HT2 receptor antagonist, induced significant inhibition of the concentration-response curve to 5-HT. 4. Contractile responses to 5-carboxamidotryptamine and 2-methyl-5-hydroxytryptamine were not affected by methiothepin and metoclopramide, respectively, whereas ketanserin significantly attenuated the contractile response to these agonists. 5. In conclusions, our study shows that 5-HT2 receptors mediate contraction of the human placental vein with no obvious role for 5-HT1-like, or 5-HT3 receptors.
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PMID:Mediation by 5-HT2 receptors of 5-hydroxytryptamine-induced contractions of human placental vein. 952 63

Serotonin (5-HT) is pruritogenic in humans and suggested to be involved in some pruritic diseases. Our experiments were carried out to determine whether an intradermal injection of 5-HT would elicit itch-associated response in mice and to elucidate the 5-HT receptor subtypes involved in this 5-HT action. 5-HT (14.1-235 nmol site(-1)) injected intradermally into the rostral back elicited scratching of the injected site, with bell-shaped dose-response relationship. The scratching induced by 5-HT (100 nmol site(-1), peak effective dose) was suppressed by capsaicin (repeated administration) and the opioid antagonist naloxone, features being similar to human itching. Scratching was also elicited by the 5-HT2 receptor agonist alpha-methylserotonin, but not by the 5-HT1A receptor agonist R(+)-8-hydroxy-N,N-dipropyl-2-aminotetralin nor the 5-HT3 receptor agonists 2-methylserotonin and 1-phenylbiganide. Scratching induced by 5-HT and alpha-methylserotonin was inhibited by peroral pretreatment with 5-HT1/2 receptor antagonists methysergide and cyproheptadine. 5-HT-induced scratching was also inhibited by intradermal injection of methysergide. Peroral pretreatment with 5-HT3 receptor antagonists ondansetron and 3-tropanyl-3, 5-dichrobenzoate did not significantly suppress 5-HT-induced scratching. The results suggest that scratching induced by intradermal injection of 5-HT is itch-associated response. The 5-HT action may be mediated at least partly by cutaneous 5-HT2 receptors.
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PMID:Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice. 1061 11

Offensive aggression in golden hamsters is inhibited by 5-hydroxytryptamine (5-HT)1A receptors and facilitated by 5-HT3 receptor activation. As such, we sought to determine whether these receptors function similarly between animals expressing an impulsive-aggressive phenotype, as compared to normal animals. Animals were screened for aggressive and impulsive choice behaviors and categorized into Low-Aggression (L-Agg) and High-Aggression (H-Agg) groups, and then tested for behavior under effective doses of 5-HT1A receptor agonist 8-hydroxy-N, N-dipropyl-2-aminotetralin (DPAT; 0.1 mg/kg and 0.3 mg/kg) or 5-HT3 receptor antagonist tropisetron (0.3 mg/kg) treatment. Low-dose DPAT treatment inhibited both behaviors in H-Agg animals, however yielding more modest effects in L-Agg animals; while high-dose DPAT effects were confounded by side effects on locomotion. Tropisetron, on the other hand, had differential effects between groups, as aggression and impulsive choice were both inhibited in H-Agg animals, while enhanced in L-Agg individuals. In addition, while the effects of the 5-HT1A receptor were limited, the broad effects of 5-HT3 receptor included repetitive and impulsive elements of behavior, pointing to the importance of the receptor's role in the modulation of these particular aspects within the phenotype.
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PMID:Differential responses to serotonin receptor ligands in an impulsive-aggressive phenotype. 2069 45