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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We investigated changes in the extracellular levels of acetylcholine (ACh) following local application of serotonergic agents to the dorsal hippocampus of freely moving rats by means of perfusion using a microdialysis technique. Perfusion of serotonin (5-HT; 10 microM, for 30 min at a rate of 3 microliters/min), dissolved in Ringer's solution containing 10 microM eserine, showed no marked effect on the extracellular levels of ACh. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 20 microM), a 5-HT1A agonist, increased ACh levels, whereas 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS-12066B; 100 microM), a 5-HT1B agonist, decreased it. Clomipramine (2 microM), an uptake inhibitor of 5-HT, had no effect on ACh levels. Following perfusion of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190; 10 microM), which is a selective 5-HT1A antagonist, the effect of 8-OH-DPAT was totally abolished, whereas CGS-12066B decreased extracellular ACh levels. 5-HT, as well as clomipramine, had a decreasing effect on ACh levels after pretreatment with NAN-190. These results indicate that the 5-HT1A receptor, which exists in the dorsal hippocampus, enhances the spontaneous ACh release, and that the mechanism of serotonergic modulation of ACh release partly depends on both the stimulatory control via the 5-HT1A receptor and the suppressive one via the 5-HT1B receptor in the dorsal hippocampus of rats.
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PMID:Hippocampal serotonin 5-HT1A receptor enhances acetylcholine release in conscious rats. 815 30

The effects of anti-idiotypic antibodies (alpha-id) that recognize serotonin [5-hydroxytryptamine (5-HT)] receptors on myenteric neurons of the guinea pig small intestine were characterized electrophysiologically, and alpha-id binding sites were located immunocytochemically. Initial applications of the alpha-id mimicked each of three actions of 5-HT: a rapid depolarization, associated with a fall in input resistance (Rin), which was inhibited by the 5-HT3 antagonists tropisetron (> or = 1 microM) and renzapride (100 microM); a slow membrane depolarization, associated with increased Rin, that was inhibited by the 5-HT1P antagonist renzapride but was unaffected by a 5-HT4 blocking concentration of tropisetron (10 microM); and a hyperpolarization, associated with decreased Rin, that was antagonized by the 5-HT1A inhibitor NAN-190. Cross-desensitization was observed between responses to 5-HT and the alpha-id. After exposure to the alpha-id, subsequent responses to the alpha-id, 5-HT, and stimulus-evoked slow excitatory postsynaptic potentials were antagonized; however, responses to carbachol and substance P were unaffected. The alpha-id thus specifically inhibits the effects of endogenously released and exogenously applied 5-HT. The alpha-id bound to sites on myenteric and submucosal neurons and a subepithelial nerve plexus. Binding of the alpha-id was blocked by 5-HT1P-, 5-HT3-, and 5-HT4-specific antagonists. We concluded that the alpha-id binds selectively to all known subtypes of 5-HT receptor in the enteric nervous system and is thus useful for investigating the gastrointestinal function of 5-HT.
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PMID:Analysis of the role of 5-HT in the enteric nervous system using anti-idiotopic antibodies to 5-HT receptors. 816 80

Modulation of long-term potentiation (LTP) and isoproterenol-induced long-lasting potentiation (ILLP) via the 5-HT1A receptor was examined in slice preparations of the rat hippocampal dentate gyrus. 8-OH-DPAT, a selective agonist of the 5-HT1A receptor, decreased population spike (PS) amplitude in these preparations, in a dose-dependent manner. Application of NAN-190, an antagonist of the 5-HT1A receptor, blocked the 8-OH-DPAT-induced decrease in PS amplitude. LTP was not affected by application of 8-OH-DPAT during tetanic stimulation (TS), while in contrast, application of NAN-190 during TS significantly augmented LTP. The NAN-190-induced enhancement of LTP was reversed by 8-OH-DPAT. In addition, a dose-dependent inhibition of isoproterenol-induced long-lasting potentiation was produced by simultaneous application of 8-OH-DPAT and isoproterenol. These results suggests that 5-HT modulates LTP in the hippocampal dentate gyrus via the 5-HT1A receptor, in an inhibitory fashion.
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PMID:Inhibitory modulation of long-term potentiation via the 5-HT1A receptor in slices of the rat hippocampal dentate gyrus. 818 86

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

We studied the effects of buspirone, a 5-HT1A receptor agonist, on head twitch behavior induced by 5-hydroxy-L-tryptophan (5-HTP) administered together with pargyline in mice. Buspirone dose dependently (0.1-10 mg/kg i.p.) enhanced head twitch behavior. This effect was blocked by (-)-propranolol and NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine hydrobromide). The enhancing effect of buspirone was also observed when mice were pretreated with p-chlorophenylalanine. These findings suggest that the enhancing effect of buspirone on head twitch behavior may be exerted through the activation of post-synaptic 5-HT1A receptors.
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PMID:Buspirone enhances head twitch behavior in mice. 820 Apr 25

Eight White Carneau pigeons were trained to discriminate 1.0 or 1.7 mg/kg of cocaine from saline. A fixed number of consecutive key peck responses on one key after the administration of cocaine resulted in 4-sec access to mixed grain. The same number of consecutive responses on the other key after saline also produced food. Different doses of cocaine and other drugs were tested to determine their ability to substitute (80% or more responding on the cocaine-appropriate key). The test drugs were selected to determine the selectivity of the cocaine discrimination in pigeons as well the role of different monoamines in mediating this behavioral effect. The drugs included other psychomotor stimulants, antidepressants, clonidine, yohimbine, other dopamine (1-(2-[bis(4-fluoro-phenyl)-methoxy]ethyl)4-3-phenylpropyl piperazine, GBR 12909) and serotonin (5-HT, sertraline) reuptake blockers, a D1 (SKF 75670), D2 (quinpirole), and 5-HT1A (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) agonist as well as the 5-HT3 antagonists, MDL 72222, LY 278584 and ondansetron. In addition, prazosin, an alpha 1 adrenergic antagonist, SCH 23390, a D1 antagonist; raclopride, a D2 antagonist and 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)butyl]piperazine (NAN-190), a putative 5-HT1A antagonist, were given in combination with cocaine to determine their ability to block the discriminative stimulus (DS) effects of cocaine, i.e., reduce drug-appropriate responding to 20% or less. The psychomotor stimulants, d-amphetamine and d-methamphetamine, completely substituted for cocaine and were similar in potency to each other and cocaine. The antidepressants I-deprenyl, imipramine, tomoxetine and bupropion also occasioned cocaine-appropriate responding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The discriminative stimulus effects of cocaine in pigeons. 822 35

A new model of 4-alkyl-1-arylpiperazines containing a terminal dihydronaphthalene fragment on the alkyl chain was synthesized in order to have mixed serotonergic and dopaminergic activity and to pursue the recent alternative approaches to the discovery of novel antipsychotic and anxiolytic agents. Title compounds were evaluated for in vitro activity on dopamine D-2 and serotonin 5-HT1A and 5-HT2 receptors by radioreceptor binding assays. They show high nanomolar affinity for 5-HT1A, moderate affinity for D-2, and low affinity for 5-HT2 receptors, and in particular, two compounds, 4-[3-(1,2-dihydro-6-methoxynaphthalen-4-yl)-n-propyl]-1-(2- methoxyphenyl)piperazine (8) and 4-[3-(1,2-dihydro-8-methoxynaphthalen-4-yl)-n-propyl]-1-(2- pyridyl)piperazine (15), show values (nM) of IC50 = 2.0 and 1.4 for 5-HT1A and IC50 = 90.6 and 119.3 for D-2, respectively. Some in vivo behavioral studies show compound 8 to be an antagonist on 5-HT1A receptors. These first findings place the new arylpiperazines on the same level as that of the azaspirone class, e.g., 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-n-butyl]piperazine (NAN-190) and buspirone.
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PMID:Mixed 5-HT1A/D-2 activity of a new model of arylpiperazines: 1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines. 1. Synthesis and structure-activity relationships. 828 7

The novel benzodioxopiperazines [4-(benzodioxan-5-yl)1-[2- (benzocyclobutane-1-yl)ethyl]piperazine] (S 14489), [4-(benzodioxan-5-yl)1-(indan-2-yl)piperazine)] (S 15535) and [4-(benzodioxan-5-yl)1-[2(indan-1-yl)ethyl]piperazine (S15931) competitively displaced the binding of [3H]-8-OH-DPAT at serotonin (5-HT)1A receptors with affinities (pKis) of 9.2, 8.8 and 8.9, respectively. These values compared favorably with those of the structurally related eltoprazine (8.0) and the proposed 5-HT1A antagonists NAN-190 (9.2), MDL 73005 EF (8.9), SDZ 216-525 (8.8), BMY 7378 (8.7), (-)-tertatolol (8.1), (-)-alprenolol (7.7), WAY 100,135 (7.5) and spiperone (6.9). The affinities of S 14489, S 15535 and S 15931 for other 5-HT receptor types (5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 and 5-HT3) were about 50 to 1000-fold lower. The spontaneous tail-flicks, flat-body posture and hypothermia mediated by an action of the 5-HT1A agonist 8-OH-DPAT at postsynaptic 5-HT1A receptors were dose-dependently and completely antagonized by S 14489, S 15535 and S15931 at doses of 0.63 to 10.0 and 2.5 to 40.0 mg/kg for s.c. and oral administration, respectively. They did not induce these responses alone, and in their presence, dose-response curves for 8-OH-DPAT were shifted in parallel to the right without loss of maximal effect. By contrast, eltoprazine, MDL 73005 EF, BMY 7378 and NAN-190 behaved as "partial" agonists and only incompletely antagonized the actions of 8-OH-DPAT in these tests. At 5-HT1A autoreceptors, S 14489, S 15535 and S 15931 acted as agonists in inhibiting striatal 5-hydroxytryptophan accumulation (0.16-2.5 mg/kg, s.c.) and in abolishing the electrical activity of the dorsal raphe nucleus (0.005-0.100 mg/kg, i.v.). Eltoprazine, BMY 7378, NAN-190 and MDL 73005 EF also behaved as agonists at these 5-HT1A autoreceptors, whereas WAY 100,135, spiperone, (-)-tertatolol, (-)-alprenolol and SDZ 216-525 inhibited neither accumulation nor firing. WAY 100,135 and spiperone antagonized the inhibition of DRN firing induced by S 14489, S 15535 and S 15931. The affinity of 15535 for dopamine D1 and D2 receptors, as well as for beta-, alpha 1- and alpha 2-adrenoceptors, was > 100-fold lower than its affinity for 5-HT1A receptors. Further, in vivo, at doses of 10.0 to 40.0 mg/kg, s.c., it showed minimal activity in tests of dopamine D2 (and D1) receptor-mediated activity. Similarly, in vivo, S 15535 was weakly active in a test of alpha 1-adrenoceptor-mediated activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Novel benzodioxopiperazines acting as antagonists at postsynaptic 5-HT1A receptors and as agonists at 5-HT1A autoreceptors: a comparative pharmacological characterization with proposed 5-HT1A antagonists. 830 75

Plasma oxytocin responses to the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone and ipsapirone, and the 5-HT2/5-HT1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) have been studied in conscious, freely moving male rats. All four compounds caused dose-related increases in plasma oxytocin concentrations after intravenous administration. Oxytocin responses to 8-OH-DPAT were significantly attenuated by pretreatment with the 5-HT1A receptor antagonist NAN-190 while responses to DOI were blocked by pretreatment with the 5-HT2/5-HT1C receptor antagonist ritanserin. Since vasopressin concentration did not change despite the marked elevation in plasma oxytocin, these results suggest that 5-HT1A and 5-HT2/5-HT1C receptors all stimulate oxytocin secretion, and this effect does not reflect a general neurohypophyseal hormone release.
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PMID:Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat. 833 26


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