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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

In rats lightly restrained in horizontal cylinders, (+/-)-3,4-methylenedioxymethamphetamine (MDMA) dose dependently (0.16-10.0 mg/kg, s.c.) elicited spontaneous tail-flicks; that is, tail-flicks in the absence of extraneous stimulation. In contrast, amphetamine over a similar dose-range was inactive. Selective inhibitors of 5-hydroxytryptamine (5-HT) uptake and carrier-mediated 5-HT release, paroxetine and citalopram, did not induce spontaneous tail-flicks themselves and blocked those induced by MDMA. In distinction, maprotiline and bupropion, selective inhibitors of noradrenaline and dopamine uptake, respectively, failed to modify the action of MDMA. Spontaneous tail-flicks elicited by MDMA were unaffected by the selective 5-HT3 receptor antagonists, ICS 205,930 and GR 38032F. They were attenuated by the mixed 5-HT1/5-HT2 receptor antagonist, methiotepin, the mixed 5-HT1A/5-HT1B receptor antagonist, (-)-alprenolol and the mixed 5-HT1A/5-HT2 receptor antagonist, spiperone, but not by the selective 5-HT1C/5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D1, D2, alpha 1, alpha 2, beta 1 and beta 2 antagonists had little influence upon induction of spontaneous tail-flicks by MDMA. These data indicate that MDMA evokes spontaneous tail-flicks in the rat via a release of 5-HT which acts at 5-HT1A receptors. Thus, 5-HT1A receptors appear to be involved in the acute functional actions of MDMA.
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PMID:Methylenedioxymethamphetamine induces spontaneous tail-flicks in the rat via 5-HT1A receptors. 167 9

To elucidate the mechanism of antinociceptive effects of calcitonin, we investigated whether receptor antagonists for various neurotransmitter receptors alter the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice. Neither naloxone, an opioid receptor antagonist, phentolamine and benextramine, alpha-adrenoceptor antagonists, nor ritanserin, a 5-HT2A receptor antagonist, inhibited the calcitonin-induced anti-aversive effects. Pindolol and (--)-propranolol, non-selective antagonists of beta-adrenoceptors and 5-HT1 receptors, 1-(2-methoxyphenyl)-4-[4-(2-phethalimido) butyl]-piperazine hydrobromide (NAN-190), a 5-HT1A receptor antagonist, 3-tropanyl-3,5-dichlorobenzoate (MDL72222) and metoclopramide, 5-HT3 receptor antagonists, significantly inhibited the calcitonin-induced anti-aversive effects. (--)-Bicuculline, a GABAA receptor antagonist, phaclofen and 5-aminovaleric acid, GABAB receptor antagonists, also attenuated the calcitonin-induced anti-aversive effects. These results suggest that beta-adrenoceptor, 5-HT1A, 5-HT3, GABAA and GABAB receptors, but not alpha-adrenoceptor, opioid nor 5-HT2A receptors, are involved in the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice.
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PMID:Neuronal mechanism of the inhibitory effect of calcitonin on N-methyl-D-aspartate-induced aversive behavior. 779 51

In previous studies, we showed that localized perfusion of the SCN region with serotonin (5-HT) or the non-selective serotonergic, quipazine, using the microdialysis technique significantly reduced the extracellular concentration of the excitatory amino acid (EAA), glutamate. The present investigation was undertaken to extend these findings by characterizing the effects of various classes of 5-HT receptor ligands on the extracellular glutamate concentration in the SCN. Localized SCN application or i.p. injection of the 5-HT1A receptor agonist, 8-OH-DPAT, during the dark phase (6 h after lights-off) significantly reduced the extracellular glutamate concentration in the SCN region from baseline levels (38.7 +/- 8.7 and 53.4 +/- 11.2%, respectively, of pretreatment values; P < 0.05). The effect of systemically applied 8-OH-DPAT was abolished by i.p. injection of the 5-HT1A receptor antagonist, NAN-190, administered 20 min before the 8-OH-DPAT. Localized perfusion of the SCN with the 5-HT1B receptor agonist, TMFPP, also reduced extracellular glutamate but to a lesser degree than 8-OH-DPAT (80.1 +/- 3.9% of pretreatment levels; P < 0.05). This effect was prevented by i.p. injection of the non-selective 5-HT receptor antagonist, metergoline 20 min before TFMPP perfusion. Localized perfusion of the SCN region with the 5-HT2 and 5-HT3 receptor agonists, alpha-methyl 5-HT and 1-phenylbiguanide, respectively, had little effect on extracellular glutamate (both P > 0.1 vs. baseline). Systemic treatment with NAN-190 alone had little effect on extracellular glutamate, however, similar treatments with metergoline or the 5-HT2 receptor antagonist, ritanserin, induced significant increases extracellular glutamate levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear region assessed using in vivo brain microdialysis. 782 May 91

5-Hydroxytryptamine (5-HT)-induced increase of intracellular Ca2+ concentration ([Ca2+]i) was monitored in cultured canine tracheal smooth muscle cells (TSMCs) using a fluorescent Ca2+ indicator Fura-2. Stimulation of TSMCs by 5-HT produced an initial transient peak followed by a sustained, concentration-dependent elevation of [Ca2+]i. The log (EC50) values of 5-HT for the peak and sustained plateau responses were -7.43 and -7.60 M, respectively. 5-HT1A and 5-HT3 receptor antagonists, NAN-190 and metoclopramide, inhibited the 5-HT-stimulated increase in [Ca2+]i with pKB values of 6.3 and 6.2, respectively, indicating that the 5-HT receptors mediating Ca2+ signal had low affinity for these receptor antagonists. In contrast, 5-HT2A receptor antagonists, ketanserin and mianserin, had high affinity in antagonizing the changes in [Ca2+]i response to 5-HT with pKB values of 8.3 and 8.3, respectively. The sustained elevation of [Ca2+]i was dependent on the presence of extracellular Ca2+. Removal of extracellular Ca2+ by addition of 2 mM EGTA during the sustained phase caused a rapid decline in [Ca2+]i to the resting level. In the absence of extracellular Ca2+, only an initial peak was observed which then declined to the resting level; the sustained elevation of [Ca2+]i could then be evoked by addition of 1.8 mM Ca2+ in the continued presence of 5-HT. Ca2+ influx was required for the changes of [Ca2+]i, since the Ca(2+)-channel blockers, diltiazem, verapamil, and Ni2+, decreased both the initial and sustained elevation of [Ca2+]i in response to 5-HT. These Ca(2+)-channel blockers also decreased the sustained elevation of [Ca2+]i when applied during the plateau phase. In conclusion, these findings indicate that the initial increase in [Ca2+]i stimulated by 5-HT acting on 5-HT2A receptors is due to the release of Ca2+ from internal stores, followed by the influx of external Ca2+ into the cells. The influx of extracellular Ca2+ partially involves a diltiazem and verapamil sensitive Ca2+ channel.
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PMID:5-Hydroxytryptamine-stimulated calcium mobilization in cultured canine tracheal smooth muscle cells. 782 73

The purpose of the present study was to examine the role of serotonin (5HT) in the discriminative stimulus effects of kappa opioids. Pigeons were trained to discriminate 5.6 mg/kg of the kappa opioid, U50,488, from water. During substitution tests, both U50,488 and another kappa opioid, spiradoline, produced > 80% responding on the U50,488-appropriate key. In contrast, the non-opioid compound, phencyclidine and several serotonergic compounds failed to substitute for the U50,488 discriminative stimulus across a wide range of doses. During combination tests, the selective 5HT1A agonist, 8-OH-DPAT (0.001-3.2 mg/kg), dose-dependently attenuated the discriminative stimulus effects of 5.6 mg/kg U50,488 and 3.2 mg/kg spiradoline. This effect was reversed by the 5HT1A antagonist, NAN-190 (0.01-1 mg/kg), in a dose-dependent manner. Buspirone (0.01-10 mg/kg), a 5HT1A partial agonist, also attenuated the discriminative stimulus effects of the training dose of U50,488 but ipsapirone, another 5HT1A partial agonist, did not. Ketanserin, a 5HT2 antagonist, and MDL72222, a 5HT3 antagonist, attenuated the effects of U50,488, whereas the 5HT1B,1C agonist, mCPP, and the 5HT2 agonist, DOI, did not. Depletion of 5HT with p-CPA also attenuated U50,488's discriminative stimulus effects. Taken together, the results suggest that serotonin release is an important component in the discriminative stimulus effects produced by kappa opioids; however, the effects of DOI and mCPP alone suggest that activation of post-synaptic 5HT receptors is not sufficient to produce the full spectrum of kappa opioid discriminative stimulus effects.
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PMID:Serotonin involvement in the discriminative stimulus effects of kappa opioids in pigeons. 787 Sep 36

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.
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PMID:5-Hydroxytryptamine receptor-mediated phosphoinositide hydrolysis in canine cultured tracheal smooth muscle cells. 801 56

5HT modulates the rhythmic locomotor output of most vertebrates by enhancing the duration and intensity of motor bursts in each cycle, but there is little clear evidence on the pharmacological profile of the 5HT receptor subtype(s) involved. In this study we extend our previous work on the role of 5HT in the development and modulation of locomotor behaviour in newly hatched Xenopus tadpoles by examining the 5HT receptor type responsible for enhancing the swimming activity in immobilized preparations. By applying a range of agonists and antagonists against different 5HT receptor subtypes, we conclude that serotonergic modulation of swimming activity is accomplished via the activation of just one receptor type with a pharmacological profile similar to the mammalian 5HT1a receptor. The effects of 5HT on burst duration (an increase) and on episode length (a decrease) are mimicked by the 5HT1a receptor agonists, 5-carboxamidotryptamine (5CT) and R(+)-8-OH-DPAT, and reversed by the 5HT1a receptor antagonist NAN-190. Agents acting at other 5HT1, as well as 5HT2 and 5HT3, receptor subtypes were without noticeable effect on the 5HT-enhanced swimming rhythm.
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PMID:Modulation of rhythmic swimming activity in post-embryonic Xenopus laevis tadpoles by 5-hydroxytryptamine acting at 5HT1a receptors. 809 Jul 92

The actions of 5-hydroxtryptamine (5-HT)1A and 5-HT4 receptor agonists on fast excitatory postsynaptic potentials (EPSPs) in myenteric neurons of guinea pig ileum were studied in vitro. Intracellular electrophysiological methods were used to record EPSPs. 5-HT (0.1 microM), 5-carboxamidotryptamine (0.001-0.1 microM), 8-hydroxydipropylaminotetralin (0.003-0.3 microM), and 5-methoxytryptamine (5-MeOT; 0.3 microM) inhibited EPSPs. Agonist inhibition of EPSPs was blocked by the 5-HT1A receptor antagonists, spiperone and NAN-190. In the presence of NAN-190 (0.3 microM), 5-HT (0.001-0.1 microM) increased EPSP amplitude. 5-MeOT (0.001-0.1 microM), renzapride (0.01-0.3 microM), cisapride (0.01-1 microM), and BIMU 8 (0.003-0.1 microM) increased EPSP amplitude but did not change the membrane potential of any neuron. EPSP potentiation induced by each agonist was blocked by the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM), but not by the 5-HT3 receptor antagonist, ondansetron (1 microM). Potentiation of fast EPSPs by 5-HT (0.1 microM) desensitized, whereas renzapride (0.1 microM) responses did not. Desensitization induced by BIMU 8 was variable. These data indicate that enteric 5-HT1A and 5-HT4 receptors function to inhibit and facilitate transmitter release, respectively. 5-HT4-mediated facilitation of ganglionic neurotransmission could contribute to the prokinetic effects of cisapride and renzapride.
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PMID:5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. 814 Dec 96

In previous studies, we showed that light-induced Fos protein expression in the ventrolateral SCN is markedly inhibited by the nonselective serotonergic, quipazine. The present experiments were undertaken to characterize the effects of various serotonin (5-HT) receptor ligands on photic signalling in the SCN. The extent of expression of light-induced Fos-like immunoreactivity (Fos-LI) in the SCN was used as a marker for this response. Exposure of hamsters to a light pulse delivered during the latter part of the dark phase (7 h after lights-off; LD 14:10) elicited an intense expression of Fos-LI in nuclei of cells situated principally in the ventrolateral region of the SCN. Pretreatment with an i.p. injection of the 5-HT1A receptor agonists, 8-OH-DPAT or buspirone, 30 min before the light pulse significantly inhibited the photic expression of Fos-LI (maximal suppression 45.7 +/- 8.1 and 43.0 +/- 1.3%, respectively, both P < 0.01 vs. vehicle controls). Treatment with the 5-HT1A receptor antagonist, NAN-190, administered 15 min before 8-OH-DPAT injection prevented the inhibitory effect of 8-OH-DPAT (100.9 +/- 6.0% vs. controls, P > 0.9). Pretreatment with the 5-HT1B receptor agonist, TFMPP, caused a small but significant suppression of Fos-LI (14.8 +/- 3.5% vs. controls, P < 0.05). In contrast to the significant 5-HT1 receptor agonist effects, pretreatment with 5-HT2 or 5-HT3 receptor agonists, alpha-methyl-5-HT and 1-phenylbiguanide had little suppressive effect on Fos-LI (7.9 +/- 2.1 and 13.0 +/- 5.0% suppression, respectively, both P > 0.1 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of light-induced C-Fos expression in the suprachiasmatic nuclei by 5-HT1A receptor agonists. 819 64


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