UNIPROT:P08908 - FACTA Search

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

Retinal input to the suprachiasmatic nuclei (SCN) and the intergeniculate leaflet (IGL) is involved in photic entrainment of mammalian circadian rhythms. The activating effects of light on firing rates of IGL cells may be regulated by serotonin (5-HT), since the IGL receives a dense serotonergic input from the midbrain raphe. We investigated the effects of 5-HT agonists and melatonin (a derivative of 5-HT) on single-unit discharges of light-sensitive cells in the hamster IGL area, using a microiontophoretic technique. 5-HT and a 5-HT1A-selective agonist, 8-OH-DPAT, potently suppressed both spontaneous and light-induced activity of IGL cells in a dose-related manner. This suppression was unchanged or potentiated by concurrently applied Mg2+, suggesting a direct action. Furthermore, the suppressive effects of both agonists were antagonized by a nonselective 5-HT antagonist, metergoline, and a 5-HT1A-directed antagonist, pindobind-5-HT1A. However, other putative 5-HT1A antagonists were weak (propranolol) or ineffective (pindolol and spiperone) in blocking the effects of 8-OH-DPAT. Neither of two 5-HT2 antagonists tested was able to block the effects of 5-HT. Melatonin generally mimicked the effects of 5-HT agonists on IGL cells, but these effects were not attenuated by 5-HT antagonists. The results indicate that both 5-HT and melatonin exert inhibitory effects on spontaneous activity and photic responses of cells in the hamster IGL, and that these effects are mediated via a 5-HT1A-like receptor and a melatonin receptor, respectively.
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PMID:Effects of serotonin agonists and melatonin on photic responses of hamster intergeniculate leaflet neurons. 831 74

1. Modulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on excitatory postsynaptic currents (EPSCs) were studied with whole-cell recordings from superficial dorsal horn (SDH) neurones in neonatal rat spinal cord slices. In one-third of SDH neurones, 5-HT induced a sustained potentiation of evoked EPSCs lasting for more than 30 min after wash-out. This potentiation was often preceded by a transient suppression of EPSCs. 2. Serotonin differentially modulated the frequency of miniature EPSCs recorded in the presence of tetrodotoxin (TTX) according to the SDH neurones, producing a transient suppression, a transient facilitation or a long-lasting facilitation. 3. The 5-HT1A-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) suppressed the amplitude of evoked EPSCs and frequency of miniature EPSCs in a reversible manner. In contrast, the 5-HT2-receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl-5-HT induced long-lasting potentiations of EPSC amplitude and miniature EPSC frequency. 4. Neither the mean amplitude nor the kinetics of miniature EPSCs were affected by 5-HT during the sustained facilitation of miniature EPSC frequency, suggesting that the facilitatory effect of 5-HT was presynaptically mediated. The 5-HT-induced long-lasting facilitation of miniature EPSC frequency was observed also in Ca(2+)-free, Mg2+ solution. 5. The long-lasting facilitation of evoked EPSC amplitude and miniature EPSC frequency by 5-HT was mimicked by the phorbol ester, phorbol 12,13-dibutyrate (PDBu), and blocked reversibly by the protein kinase C (PKC) inhibitor, calphostin C. Forskolin applied together with 3-isobutyl-1-methylxanthine (IBMX) had no effect on the evoked EPSCs. 6. We conclude that serotonin can induce a long-lasting facilitation of evoked EPSCs and spontaneous release of excitatory transmitter at SDH synapses of rat spinal cord. Our results suggest that intracellular PKC linked to the 5-HT2 receptor may mediate this effect by directly activating the exocytotic machinery.
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PMID:Long-lasting synaptic facilitation induced by serotonin in superficial dorsal horn neurones of the rat spinal cord. 873 96

Pancreatic ganglia contain 5-hydroxytryptamine (5-HT)-immunoreactive axons, some of which are extensions of myenteric neurons located in the pyloric antrum and proximal duodenum. The present study investigated the effect of 5-HT on the membrane potential of cat pancreatic ganglion neurons by means of intracellular recordings in vitro. Pressure application of 5-HT evoked a fast depolarization in 29 of 147 neurons and a slow depolarization in 89 of 147 neurons. A biphasic response was observed in 10 of 108 neurons. The 5-HT-induced slow depolarizing response was not altered in a low Ca2+ (0.1 mM), high Mg2+ (15 mM) solution nor by hexamethonium (10(-4) M) or atropine (10(-6) M). The fast depolarizing response was associated with a decrease of membrane input resistance (-17.2%). The slow depolarizing response was associated with either a decrease (-19.6%) in 24, an increase (+25.0%) in 20, or without a detectable change of membrane input resistance in 10 out of 54 neurons tested. Conditioning hyperpolarization increased the amplitude of both fast and slow depolarizing responses. A low Na+ (68.5 mM) solution and a high K+ (23.5 mM) solution significantly reduced the amplitude of the slow depolarizing response. A low Cl- (9.6 mM) solution had no significant effect on the slow depolarization. The 5-HT3 receptor antagonist MDL 72222 (Bemesetron) blocked the 5-HT-evoked fast depolarizing response. BRL 24924 (Renzapride) and 5 HT-DP, antagonists for the putative 5-HT1P receptor, blocked the slow depolarizing response. The 5-HT3 receptor agonist 2-methyl-5-HT evoked a fast depolarizing response and MCPP, an agonist for the putative 5-HT1P receptor, evoked a slow depolarizing response. Spiperone (a 5-HT1A receptor antagonist) and mianserin (a 5-HT2 receptor antagonist) had no effect on either depolarizing response to 5-HT. The results show that pancreatic ganglion neurons responded to 5-HT with fast and slow depolarizing responses. The data suggest that these responses were mediated by the 5-HT3 receptor and the putative 5-HT1P receptor, respectively.
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PMID:5-Hydroxytryptamine depolarizes neurons of cat pancreatic ganglia. 886 89

The saturation parameters and the pharmacological characteristics of the binding of the serotonin 1A (5-HT1A) receptor agonist [3H]8-hydroxy-2-(di-N-propylamino)tetralin ([3H]8-OH-DPAT), as well as the effects of nucleotides and divalent cations (Mg2+, Mn2+) on it, were compared in some human postmortem brain regions: the main cortical areas, hippocampus and striatum. [3H]8-OH-DPAT labelled a single population of recognition sites with the highest maximal capacity (Bmax) in the hippocampus and the lowest affinity in the striatum. Among the various cortical areas, the frontal cortex exhibited the highest Bmax. The pharmacological profile of the [3H]8-OH-DPAT binding sites was consistent with the labelling of the 5-HT1A receptor in the hippocampus and cortex, whereas the striatal site shared strong similarity to the presynaptic serotonin transporter. Modulation of [3H]8-OH-DPAT binding by divalent cations and nucleotides was detectable and stable in autopsy brains. In particular, nucleotide effects were area-dependent: guanosine thiotriphosphate (GTP gamma S) reduced [3H]8-OH-DPAT binding to the same extent in the hippocampus and frontal cortex, while having no effect in the striatum. Divalent cation effects depended also upon the brain area: in the striatum, they inhibited [3H]8-OH-DPAT binding, while stimulating it in the hippocampus and, with less extent, in the frontal cortex. In summary, these findings suggest that the [3H]8-OH-DPAT binding and its modulatory parameters in human brain tissues seem to show similarities but also some differences with respect to those determined in the rat brain. Furthermore, postmortem stability of GTP and divalent cation sensitive 5-HT1A receptors underlines the need for further studies on the regulatory and functional properties of this receptor in the human brain.
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PMID:Further characterisation of [3H]8-hydroxy-2-(di-N-propylamino)tetralin binding sites in human brain postmortem. 901 62

The ligand binding characteristics of the recombinant human 5-HT1A receptor stably expressed in a Chinese Hamster Ovary (CHO) cell line are described using a selective agonist, [3H]8-OH-DPAT, and a novel antagonist radioligand, [3H]WAY-100635. The association of [3H]WAY-100635 was a time- and temperature-dependent process. Mn2+ > Ca2+ > Mg2+ reduced the specific [3H]WAY-100635 binding in a concentration-dependent manner, whereas Na+ and K+ were ineffective. Scatchard analyses revealed a homogeneous population of [3H]WAY-100635 recognition sites (Kd = 0.32 nM; Bmax = 162 fmol/mg of protein). Addition of divalent cations to the incubation medium produced a two-fold decrease in the binding affinity of [3H]WAY-100635 with no significant change in Bmax; GTP gamma S had no effect on Kd or Bmax parameters. [3H]WAY-100635 displayed a higher affinity (2-3 fold) for the 5-HT1A site when compared with [3H] 8-OH-DPAT binding under similar incubation conditions. Furthermore, [3H] 8-OH-DPAT labelled approximately 53-61% of total 5-HT1A sites recognised by [3H]WAY-100635. The competition binding profiles of [3H]WAY-100635 and [3H]8-OH-DPAT were highly correlated and consistent with the recognition of 5-HT1A receptors. Agonist competition curves with [3H]WAY-100635 were best-resolved into high- and low-affinity binding states, whereas partial agonist and antagonist curves were best-fit to one-site binding models. A significant correlation between the respective affinities of a range of agonists and antagonists at recombinant human and rodent hippocampal 5-HT1A binding sites (previously published) was also observed using [3H]WAY-100635 (r = 0.92; P < 0.0005) and [3H]8-OH-DPAT (r = 0.96; P < 0.0005). The availability of a novel, high-affinity antagonist radioligand, [3H]WAY-100635, will provide a useful tool for the further characterisation of 5-HT1A receptor pharmacology.
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PMID:Pharmacological characterization of recombinant human 5-hydroxytryptamine1A receptors using a novel antagonist radioligand, [3H]WAY-100635. 904 68

Hippocampal dentate gyrus reactivity to perforant path (PP) stimulation in the anesthetized rat was enhanced after systemic administration of the serotonin-releasing drug fenfluramine (FFA). This effect of FFA was mimicked by local application of the drug via the recording pipette, indicating that the effect of FFA is mediated by release of serotonin from intrahippocampal serotonergic terminals. The 5-HT1a antagonist NAN-190 and the 5-HT1b agonist CGS-12066-B, applied both systemically and locally, blocked the effect of FFA. This blocking action was not shared by the 5-HT2-4 receptor agonists or antagonists tested. The 5-HT1a receptor agonist 8-OH-DPAT, applied systemically, caused a marked reduction in population spike responses to PP stimulation, whereas an opposite effect was produced by local application of this drug. The effect of peripheral application of 8-OH-DPAT was blocked by depletion of serotonin. The local effect of FFA was blocked by a reducing neurotransmitter release with a pipette containing 10 mM Mg2+. Finally, local application of the GABA antagonist picrotoxin also enhanced population spike response to PP stimulation, and the effects of picrotoxin and FFA occluded. These results indicate that serotonin released from terminals in the hippocampus activates a 5-HT1a receptor on interneurons that suppresses their activity and thus enhances dentate granular cell population spike response to PP stimulation.
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PMID:Serotonin 5-HT1A receptors modulate hippocampal reactivity to afferent stimulation. 920 40

The present study was undertaken to compare the properties of the [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) binding site in the dorsal raphe nucleus with the hippocampal 5-HT1A receptor. In both tissues inclusion of 1 mM Mg2+ enhanced specific [3H]8-OH-DPAT binding, while 1 mM GTP decreased radioligand binding. [3H]8-OH-DPAT appears to bind to a single population of binding sites in both the hippocampus and the dorsal raphe nucleus, although the K(d) for the radioligand at the dorsal raphe site was five times that observed at the hippocampal 5-HT1A receptor. Similarly, although 5-HT and selective 5-HT1A receptor ligands displayed high affinity for the [3H]8-OH-DPAT binding site in the dorsal raphe nucleus, the affinity at the dorsal raphe site was less than that observed at the hippocampal 5-HT1A receptor. 8-OH-DPAT inhibited forskolin-stimulated adenylyl cyclase activity in the hippocampus, but did not alter enzyme activity in the dorsal raphe nucleus. Conversely, 8-OH-DPAT inhibited the accumulation of [3H]inositol phosphates in the dorsal raphe nucleus, but not in the hippocampus. An inhibition of phosphoinositide hydrolysis in the dorsal raphe nucleus also was found with the putative 5-HT1A receptor selective ligands, flesinoxan and gepirone. However, addition of another putative 5HT1A receptor selective ligand, buspirone, did not alter the generation of [3H]inositol phosphates, but blocked the inhibitory effect of 8-OH-DPAT on phosphoinositide hydrolysis. These studies demonstrate that the 8-OH-DPAT binding site in the dorsal raphe nucleus displays a binding profile which is similar to the hippocampal 5-HT1A receptor, but unlike this 5-HT1A receptor the binding site in the dorsal raphe nucleus is negatively coupled to phosphoinositide turnover.
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PMID:[3H]8-OH-DPAT labels a 5-HT site coupled to inhibition of phosphoinositide hydrolysis in the dorsal raphe. 921 90

The regulation by N-methyl-D-aspartate (NMDA) and 5-HT1A receptors of the endogenous gamma-aminobutyric acid (GABA) release was investigated in slices of the guinea pig dentate gyrus. The release of GABA was increased in a concentration-dependent fashion by NMDA. The release of GABA evoked by NMDA was Ca2+-dependent, tetrodotoxin-resistant, Mg2+-sensitive and inhibited by MK-801, a selective non-competitive NMDA receptor antagonist. These results suggest that the NMDA receptor present on GABAergic neurons is involved in the stimulatory regulation of GABA release. The release of GABA was increased concentration-dependently by NAN-190, a 5-HT1A receptor antagonist, but was not affected by 8-OH-DPAT, a 5-HT1A receptor agonist. The release of GABA evoked by NAN-190 was Ca2+-dependent, tetrodotoxin-resistant and inhibited by 8-OH-DPAT. These results suggest that the 5-HT1A receptor present on GABAergic neurons is involved in the inhibitory regulation of GABA release. The release of GABA evoked by NMDA from the dentate gyrus was inhibited by pretreatment with 8-OH-DPAT. The release of GABA evoked by NAN-190 was inhibited by pretreatment with MK-801. The release of GABA evoked by NMDA from the dentate gyrus was augmented by the concurrent application of NAN-190. Taken together, the results indicate that the NMDA receptor and the 5-HT1A receptor, which are both located on GABAergic neurons in the guinea pig dentate gyrus, exert stimulatory and inhibitory regulation of neuronal GABA release, respectively.
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PMID:Regulation of GABA release via NMDA and 5-HT1A receptors in guinea pig dentate gyrus. 924 72

The anti-epileptiform effect of serotonin was characterized in cellular models of epilepsy using electrophysiological recording techniques. In the bicuculline model, both serotonin (20 microM) and its 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 microM) completely blocked the epileptiform discharge and caused membrane hyperpolarization and reduction in input resistance. These effects were completely antagonized by the 5-HT1A receptor antagonist N-t-butyl-3(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenyl-propanamid e(WAY 100135) (10 microM). Epileptiform discharge induced by positive current injection was also blocked by serotonin. The presence of WAY 100135 renders serotonin ineffective in the same model. In the bicuculline model, epileptiform discharge blocked by serotonin reappeared and was also intensified when BaCl2 was added to the medium. To rule out the possibility of serotonin-induced hyperpolarization strengthening the inhibitory effect of endogenous Mg2+ on glutamate N-methyl-D-aspartic acid (NMDA) receptor we studied the antiepileptic effect of serotonin in the 0 Mg2+ model. Spontaneous activity and evoked bursts seen with the 0 Mg2+ model were completely blocked by serotonin. WAY 100135 completely antagonized serotonin effects in this model as well. This study provides evidence suggesting that in rat CA1 pyramidal neurons, serotonin can inhibit epileptiform activity in a variety of accepted epilepsy cellular models and that inhibition of epileptiform bursts by serotonin may be mediated by activation of the 5-HT1A receptor subtype.
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PMID:Serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in CA1 pyramidal neurons. 951 42

Whole cell patch recordings were made from rostral ventrolateral medullar (RVLM) neurons of brain-stem slices from 8- to 12-day-old rats. By superfusion or pressure ejection to RVLM neurons, 5-hydroxytryptamine (5-HT) elicited three types of membrane potential changes: a slow hyperpolarization (5-HTH), a slow depolarization (5-HTD) and a biphasic response, which persisted in a tetrodotoxin (TTX, 0.3 microM)-containing solution. 5-HTH were accompanied by a decrease of input resistance in the majority of responsive neurons. Hyperpolarization reduced and depolarization increased the 5-HTH; the mean reversal potential was -92.3 mV in 3.1 mM and shifted to -69.3 mV in 7 mM [K+]o. Barium (Ba2+, 0.1 mM) but not tetraethylammonium (TEA, 10 mM) suppressed 5-HTH. The 5-HT1A receptor agonist (+/-)-8-hydroxy-dipropylamino-tetralin (8-OH-DPAT; 5-50 microM) hyperpolarized RVLM neurons. The 5-HT1A antagonist pindobind-5-HT1A (PBD; 1-3 microM) and the 5-HT2/5-HT1 receptor antagonist spiperone (1-10 microM) suppressed 5-HTH and the hyperpolarizing phase of biphasic responses; the 5-HT2 receptor antagonist ketanserin (3 microM) was without significant effect. 5-HTD were associated with an increase or no apparent change of input resistance in RVLM neurons. Hyperpolarization of the membrane decreased or caused no apparent change in 5-HTD. 5-HTD were reduced in an elevated [K+]o (7.0 mM) solution and > 60% in a low Na+ (26 mM) solution and were not significantly changed in a low Cl- (6.7 mM) or Ca(2+)-free/high Mg2+ (10.9 mM) solution. The 5-HT2 receptor agonist alpha-methyl-5-HT (50 microM) depolarized RVLM neurons, and the 5-HT2 antagonist ketanserin (1-10 microM) attenuated the 5-HTD and the depolarizing phase of biphasic responses, whereas the 5-HT1A receptor antagonist PBD (2 microM) was without effect. Inclusion of the hydrolysis resistant guanine nucleotide GDP-beta-S in patch solution significantly reduced the 5-HTH as well as the 5-HTD. The present study shows that, in the immature rat RVLM neurons, 5-HT causes a slow hyperpolarization and depolarization probably by interacting with 5-HT1A and 5-HT2 receptors, which are G-proteins coupled. 5-HTH may involve an increase of an inwardly rectifying K+ conductance, and 5-HTD appear to be caused by a decrease of K+ conductance and/or increase of nonselective cation conductance.
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PMID:5-Hydroxytryptamine responses in immature rat rostral ventrolateral medulla neurons in vitro. 974 19

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