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

Multiple extracellular recording electrodes were used to study the intra- and interhemispheric spread of stimulus-evoked epileptiform responses in adult mouse neocortical slices. Bath application of 20 microM bicuculline methiodide induced epileptiform activity that propagated at approximately 0.08 m/s over several millimeters in rostro-caudal and medio-lateral direction within the ipsilateral hemisphere and across the corpus callosum to the contralateral hemisphere. A vertical incision from layer II to subcortical regions did not prevent the spread to remote cortical regions, indicating that layer I plays a major role in the lateral propagation of epileptiform activity. The intra- and interhemispheric spread was not influenced by application of an N-methyl-d-aspartate (NMDA) receptor antagonist, but blocked by an antagonist acting at the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor. The potential role of potassium channel activation in controlling the generation or spread of epileptiform activity was tested by applying the potassium channel opener cromakalim and the serotonin type 1A (5-HT1A) receptor agonist (+/-)-8-hydroxydipropylaminotetralin (8-OH-DPAT) to the disinhibited slices. Whereas cromakalim reduced the neuronal excitability and blocked all epileptiform responses, 8-OH-DAPT did not affect the activity pattern. Our results suggest that propagating epileptiform activity in disinhibited neocortical structures is predominantly mediated by activation of AMPA receptors and controllable by activation of a voltage-dependent potassium current.
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PMID:Pattern and pharmacology of propagating epileptiform activity in mouse cerebral cortex. 974 72

Using intracellular recordings, we have studied the action of 5-hydroxytryptamine (5-HT) on slices of human temporal, occipital and frontal cortex maintained in vitro. The recordings were usually made 1.2 to 1.5 mm down from the pial surface, in or around layer III. The action of 5-HT (30-50 microM) was studied on 21 cells (from 12 individuals) which had electrophysiological characteristics of glutamatergic pyramidal neurones. 5-HT depolarised the majority (11) of these cells with a median response of 5 mV. It produced a hyperpolarising response in five neurones (median=-4 mV) and a combined hyperpolarising/depolarising response in two others. No response was detected in three cells. The depolarising response was probably mediated by reducing a resting potassium conductance. Ketanserin (0.1 and 1.0 microM) and spiperone (1 microM) reduced the response indicating that it was likely mediated by 5-HT2A receptors. The hyperpolarising response was associated with the opening of ion channels and was blocked by the selective 5-HT1A receptor antagonist WAY-100635 (100 nM). 5-HT inhibited spontaneous synaptic potentials. This effect was reduced by ketanserin (1 microM) but not by WAY-100635 (100 nM). It is concluded that human neocortical neurones in vitro can be depolarised via 5-HT2A receptors and hyperpolarised via 5-HT1A receptors.
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PMID:Actions of 5-HT on human neocortical neurones in vitro. 1037 81

Recently we reported that rat taste receptor cells respond to the neurotransmitter serotonin with an inhibition of a calcium-activated potassium current [17]. In the present study, this observation is confirmed and extended by studying the effects of an array of serotonergic agonists on membrane properties, calcium-activated potassium current, and voltage-dependent sodium current in taste receptor cells using the patch-clamp recording technique in the whole-cell configuration. Serotonergic inhibition of calcium-activated potassium current was mimicked by the agonists N-(3-trifluoromethylphenyl)piperazine and by (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene. Both produced reversible inhibition of K(Ca) as well as significantly increasing the input resistance of the cell. The agonists 1-(1-naphthyl)piperazine and buspirone (both serotonin receptor 1A agonists) were similarly effective in reducing K(Ca). Outward current was unaffected by application of phenylbiguanide, a serotonin receptor 3 agonist, though current was affected by subsequent application of (+/-)-2-dipropylamino-8-hydroxy-1,2,3, 4-tetrahydronaphthalene. Two agonists-N-(3-trifluoromethylphenyl)piperazine and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene-were also tested on voltage-dependent sodium currents; both were effective and reversible in reducing its magnitude at a variety of applied potentials. These data are consistent with the notion that serotonin effects in rat taste receptor cells are mediated by serotonin 1A receptors, though other receptor subtypes may be additionally expressed. Serotonin may affect the taste cell electrical properties during active stimulation in a paracrine fashion.
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PMID:Serotonergic agonists inhibit calcium-activated potassium and voltage-dependent sodium currents in rat taste receptor cells. 1063 Sep 28

The spontaneous withdrawal from morphine in morphine-dependent rats significantly decreased the duration of active interaction in social interaction test and the number of licks during the shock-punished period in Vogel's conflict procedure, which were attenuated by buspirone, a 5-HT1A agonist, as well as para-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Naltrexone (NTX), a potent opioid receptor antagonist, also dose- and time-dependently reduced both indices mentioned above, which was blocked by morphine or PCPA and was enhanced by 5-hydroxytryptophan, a precursor of 5-HT. In the test of neurotransmitter releases in rat brain slices, both morphine-withdrawal and NTX enhanced high potassium(30mM)-induced 5-HT release in slices of the area of the raphe nucleus. These results suggested that both morphine-withdrawal and NTX produced anxieties in morphine-dependent and normal rats, respectively, which were mediated by the central 5-HTergic neurotransmission. Central opioidergic neurons inhibited 5-HTergic neurons tonically and presynaptically. Such an effect was reduced or blocked by NTX, or during morphine-withdrawal, and 5-HTergic neurons were disinhibited, leading to a state of anxiety.
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PMID:[Regulation of the central opioidergic nervous system on the emotional state of anxiety and its possible mechanisms]. 1092 Oct 76

Thirteen [(aryl/heteroaryl-piperazinyl)alkyl]benzotriazoles were prepared as potential trazodone- and buspirone-like drugs. The synthesized compounds displayed from moderate to good affinity to the serotonin 5-HT1A receptor and only modest or poor affinity to the dopamine D2 receptor, similar to buspirone. The introduction of substituents on the benzotriazole ring did not improve the affinity to the 5-HT1A receptor, compared to the previously described unsubstituted derivatives. In a general pharmacological screening, which concerned only three of these compounds so far (5, 7 and 13), several in vitro and in vivo activities were observed. The guinea pig ileum contractions, induced either electrically or by several agonists, were strongly inhibited; at higher concentrations also the spontaneous tone of the guinea pig trachea was reduced. Compound 13 exhibited good analgesic activity in mice in the formalin-induced algesia and in the writhing test. The same at 30 mg kg(-1) p.o. also displayed antihypertensive activity probably related to calcium channel blockade and adrenergic alpha1 antagonism. In binding assays, 13 showed a IC50 = 580 nM for displacing [3H]prazosin from alpha1 receptor. Finally, compound 5 (and, to a minor extent, compound 13) protected mice against potassium cyanide induced hypoxia.
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PMID:Synthesis and pharmacological evaluation of aryl/heteroaryl piperazinyl alkyl benzotriazoles as ligands for some serotonin and dopamine receptor subtypes. 1142 Dec 54

Serotonin (5-hydroxytryptamin, 5-HT) is localized in taste bud cells of vertebrates. Effects of the external application of 5-HT on the membrane currents of frog taste receptor cells (TRCs) were investigated using patch-clamp technique in whole-cell configuration. The 5-HT (0.1-1 micro m) and 5-HT1A receptor agonist (+/-)-8-OH-2-(D1-n-propyl-amino)tetralin (8-OH-DPAT) (1-20 micro m) inhibited both voltage-gated sodium current (INa) and voltage-gated potassium current (IK) in 50% of TRCs, but potentiated IK without any significant effect on INa in another subset of 18% of TRCs. Voltage-gated currents in the residual TRCs were not affected by 5-HT or 8-OH-DPAT. External application of 10 micro m forskolin and 300 micro m 8-cpt cAMP [8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate] mimicked the inhibitory effect of 5-HT and 8-OH-DPAT on IK and INa while internal dialysis with 50 micro m protein kinase A inhibitor prevented the 5-HT-mediated inhibitory effects on IK and INa in TRCs. Internal dialysis of TRCs with high Ca2+-pipette solution (1 micro m) increased the IK in 58% of TRCs. The 5-HT reversibly increased the [Ca2+]i in 17% of TRCs when measured by Ca2+-imaging using a Ca2+-sensitive dye (fura-2 AM). These results suggest that 5-HT differentially modulates the voltage-gated membrane currents in different subsets of TRCs.
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PMID:Serotonin differentially modulates the electrical properties of different subsets of taste receptor cells in bullfrog. 1227 38

The modulatory effects of serotonin mediated by 5-HT1A receptors in adult spinal motoneurons were investigated by intracellular recordings in a slice preparation from the turtle. In current-clamp mode, activation of 5-HT1A receptors by 8-OH-DPAT led to depolarization and an increase in input resistance in most motoneurons but caused hyperpolarization and a decrease in input resistance in the remaining smaller fraction of cells. When slices were preincubated in medium containing the 5-HT1A receptor antagonist WAY-100635, 8-OH-DPAT had no effect. In voltage-clamp mode, with 1 mM CsCl in the bathing medium, 8-OH-DPAT consistently inhibited a leak current that was sensitive to extracellular acidification and anandamide, a TASK-1 channel blocker. In medium with a low pH, as in the presence of anandamide, 8-OH-DPAT had no effect. Our results show that activation of 5-HT1A receptors contributes to the excitatory effect of serotonin on spinal motoneurons by inhibition of a TASK-1 potassium channel leading to depolarization and increased input resistance.
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PMID:5-HT1A receptors increase excitability of spinal motoneurons by inhibiting a TASK-1-like K+ current in the adult turtle. 1262 70

The effects of dopamine (DA) on the function of human 5-HT1A receptors expressed in Xenopus oocytes and CHO-K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5-HT receptors (5-HT1A, 5-HT2C, and 5-HT3) were studied comparatively in Xenopus oocyte expression system. Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. Maximal responses induced by DA were 85 +/- 4% of maximal 5-HT currents and DA responses were blocked by the specific 5-HT1A antagonist, WAY-100635 (50 nM). In CHO-K1 cells expressing 5-HT1A receptors, 5-HT and DA inhibited the specific binding of selective antagonist [3H]-8-OH-DPAT with IC50 values of 10.2 nM and 1.4 microM, and both 5-HT and DA inhibited the forskolin-induced accumulation of cAMP. In oocytes expressing 5-HT2C receptors, 5-HT and DA induced inward currents with respective EC50 values of 6.2 nM and 67.7 microM. Magnitudes of maximal DA induced currents were 42 +/- 3% of maximal 5-HT responses and blocked by the 5-HT2 antagonist, piperazine (1 microM). In oocytes expressing 5-HT3 receptors, 5-HT and DA induced fast inward currents with respective EC50 values of 2.1 microM and 266.3 microM. Maximal DA induced currents were 37 +/- 3% of maximal 5-HT responses and blocked the specific 5-HT3 antagonist LY-278584 (0.1 microM). Comparison of the potencies and efficacies of 5-HT and DA indicated that the relative potency of DA increased in the order of 5-HT3 > 5-HT1A > 5-HT2C, and relative efficacy increased in the order of 5-HT1A > 5-HT2C > 5-HT3. These results suggest that although DA activates different subtypes of human 5-HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors.
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PMID:Direct activation by dopamine of recombinant human 5-HT1A receptors: comparison with human 5-HT2C and 5-HT3 receptors. 1455 35

Small-conductance calcium-activated potassium channels (SK) are responsible for the medium afterhyperpolarisation (mAHP) following action potentials in neurons. Here we tested the ability of serotonin (5-HT) to modulate the activity of SK channels by coexpressing 5-HT1A receptors with different subtypes of SK channels (SK1, SK2, and SK3) in Xenopus laevis oocytes. SK channels were activated by intracellular injection of Cd2+. Subsequent activation of 5-HT1A receptors by 8-OH-DPAT always produced an inhibition of the SK current, showing the existence of a specific pathway between the receptor and the ion channel. To investigate the physiological relevance of this pathway, we characterized the mAHP present after action potentials in spinal motoneurons recorded in a slice preparation from the lumbar spinal cord of the adult turtle. By performing current and voltage clamp recordings, we showed that 8-OH-DPAT specifically inhibited the fraction of the AHP mediated by SK channels. We conclude that the activity of SK channels is modulated by activation of serotonergic receptors.
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PMID:5-HT1A receptors modulate small-conductance Ca2+-activated K+ channels. 1552 Oct 63

Agonists at G-protein-coupled receptors in neurons of the dorsal raphe nucleus (DRN) of knock-out mice devoid of the serotonin transporter (5-HTT(-/-)) exhibit lower efficacy to inhibit cellular discharge than in wild-type counterparts. Using patch-clamp whole-cell recordings, we found that a G-protein-gated inwardly rectifying potassium (GIRK) current is involved in the inhibition of spike discharge induced by 5-HT1A agonists (5-carboxamidotryptamine (5-CT) and (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT); 50 nM-30 microM) in both wild-type and 5-HTT(-/-) female and male mice. These effects were mimicked by 5'-guanylyl-imido-diphosphate (Gpp(NH)p; 400 microM) dialysis into cells with differences between genders. The 5-HTT(-/-) knock-out mutation reduced the current density induced by Gpp(NH)p in females but not in males. These data suggest that the decreased response of 5-HT1A receptors to agonists in 5-HTT(-/-) mutants reflects notably alteration in the coupling between G-proteins and GIRK channels in females but not in males. Accordingly, gender differences in central 5-HT neurotransmission appear to depend-at least in part-on sex-related variations in corresponding receptor-G protein signaling mechanisms.
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PMID:Gender-dependent regulation of G-protein-gated inwardly rectifying potassium current in dorsal raphe neurons in knock-out mice devoid of the 5-hydroxytryptamine transporter. 1701 26


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