Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of LSD (d-lysergic acid diethylamide) on rat facial motoneurons were compared to those of 5-hydroxytryptamine (5-HT) in brain slices by means of current clamp and single-electrode voltage-clamp recordings. As previously reported, 5-HT, in part by decreasing a resting potassium conductance, produced a reversible depolarization (approximately 5 mV), an increase in input resistance, and an enhancement in electrical excitability. LSD also produced an increase in electrical excitability, although with a much slower onset and longer duration. However, in contrast to 5-HT, LSD produced only a slight depolarization (1-2 mV). Moreover, in the presence of LSD the depolarizing effect of 5-HT was markedly attenuated. The 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced effects intermediate between LSD and 5-HT. The LSD-induced increase in electrical excitability was completely reversed by spiperone, a 5-HT2/5-HT1A antagonist, and by ritanserin, a 5-HT2/5-HT1C antagonist; the effects of 5-HT were also reduced by these 2 antagonists, but complete blockade did not occur at the concentrations and durations tested. Surprisingly, LSD was found to enhance the hyperpolarization-activated nonspecific cation current Ih to a greater extent than did 5-HT; this enhancement was blocked by both spiperone and ritanserin. These results indicate that, despite having low efficacy relative to 5-HT in decreasing resting potassium conductance, LSD has high efficacy in enhancing the Ih current in rat facial motoneurons; possible mechanisms for this difference are discussed.
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PMID:LSD has high efficacy relative to serotonin in enhancing the cationic current Ih: intracellular studies in rat facial motoneurons. 844 21

1. The serotonin1A (5-HT1A) receptor is coupled to an inwardly rectifying potassium current (IKir) via a G protein. The identity of the G-protein subtype was investigated with 2 10-amino acid peptides derived from the carboxyl (C) terminus of the alpha-subunits of the Go1 and Gi2 proteins (G alpha o1 and G alpha i2). The synthetic decapeptides were applied by intracellular perfusion during whole cell recording from dentate granule cells in the hippocampal slice preparation. 2. Bath application of 5-HT produced an IKir, which was blocked by the selective 5-HT1A receptor antagonist, pindobind5-HT1A. The G alpha o1 peptide inhibited the 5-HT1A IKir by 60 +/- 7% (mean +/- SE; t = 30 min), whereas the G alpha i2 peptide had no effect. The G alpha o1 peptide produced a slowly developing outward current that was not observed in the absence of peptide or in the presence of the G alpha i2 peptide. 3. The results indicate that G alpha o1 and not G alpha i2 modulates the 5-HT1A IKir in hippocampal granule cells. They also suggest that G alpha o1 occludes the 5-HT1A response by direct activation of the IKir. The intracellular perfusion of synthetic G alpha peptides provides a new approach to identify the G-protein subtype(s) in a receptor-mediated electrophysiological response.
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PMID:G alpha o1 decapeptide modulates the hippocampal 5-HT1A potassium current. 859 8

Based on sequence homology with the rat atrial G protein-coupled muscarinic potassium channel (GIRK1 or KGA1/KGB1), a human cDNA encoding a G protein-activated inwardly rectifying K+ channel (HGIRK1) was isolated. The cDNA encodes a protein of 501 amino acids and shares 99% identity to rat GIRK1 in its total amino acid sequence. Southern blot analysis of genomic DNA indicates a high degree of conservation among various species. In the human population a useful NlaIII restriction fragment length polymorphism was found in the coding sequence of HGIRK1. Co-expression of HGIRK1 and the 5-HT1A receptor in Xenopus oocytes resulted in opening of the channel upon treatment with serotonin. HGIRK1 currents showed strong inward rectification and could be blocked by extracellular Ba2+. Northern blot analysis shows that HGIRK1 expression in human is most abundant in the brain, while lower levels are round in kidney and heart.
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PMID:Cloning of a G protein-activated inwardly rectifying potassium channel from human cerebellum. 880 10

Central administration of galanin dose-dependently (minimum effective dose, M.E.D. = 1 nmol) blocked the hypothermia induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), in mice. This inhibitory effect was reversed by pretreatment with the galanin receptor antagonist galantide (0.3 nmol) and also by pretreatment with the ATP-sensitive potassium channel blockers glibenclamide (10 nmol) and gliquidone (10 nmol). The hypothermic response to 8-OH-DPAT was also blocked by the 5-HT1A receptor antagonist (N-(2,4(2-methoxyphenyl)-1-piperazinyl)ethyl-N-(2-pyridinyl)cyclohexane, (WAY 100,635, M.E.D. = 0.01 mg/kg s.c.), and the centrally acting muscarinic receptor antagonist scopolamine (M.E.D. = 10 mg/kg i.p.) but not the peripheral muscarinic receptor antagonist N-methylscopolamine. 8-OH-DPAT (0.5 mg/kg s.c.) also decreased cortical and hypothalamic 5-HT (5-hydroxytryptamine, serotonin) metabolism, an effect which was not blocked by pretreatment with galanin (0.3-3 nmol intracerebroventricular, i.c.v.). Neither did galanin (0.03-3 nmol/5 microliters i.c.v.) affect basal 5-HT metabolism in these brain regions. Furthermore, pretreatment in vitro of mouse cortical membranes with galanin (10 or 1000 nM) had no effect on 5-HT1A receptor affinity, Bmax or pharmacology determined using [3H]8-OH-DPAT. These results suggest that the inhibition of 8-OH-DPAT induced hypothermia by galanin is probably not mediated by an interaction with 5-HT1A receptors but more likely by blocking the indirect activation by 8-OH-DPAT of central cholinergic pathways involved in temperature regulation.
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PMID:Effects of galanin on 8-OH-DPAT induced decrease in body temperature and brain 5-hydroxytryptamine metabolism in the mouse. 899 1

Little is definitively known of the identity or actions of neurotransmitters utilized within mammalian taste buds. Serotonin has been immunocytochemically localized to taste cells of several species but its physiological actions are unknown. Using whole-cell patch clamp recordings on dissociated posterior rat taste cells, data are presented to suggest that exogenously applied serotonin inhibits a calcium-activated potassium current by up to 50%. This current, best visualized at depolarized holding potentials, is both apamin- and charybdotoxin-sensitive. Approximately 60% of the tested taste cells were serotonin sensitive. This inhibition was mimicked by N-(3-trifluoromethylphenyl)piperazine (TFMPP), a general serotonin receptor agonist, by 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, but not by phenylbiguanide, a 5-HT3 receptor agonist. These are the first data to establish a physiological effect of serotonin on mammalian taste cells.
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PMID:Serotonin inhibits calcium-activated K+ current in rat taste receptor cells. 935 53

Serotonin (1-40 microM) reduced input resistance by 20.6 +/- 6% and hyperpolarized stellate and pyramidal neurons of layers two and three of the lateral entorhinal cortex. 5-Carboxamidotryptamine, a 5-HT1 agonist, and the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin mimicked the action of serotonin. The reversal potential of 5-HT-mediated hyperpolarizations was sensitive to the extracellular K+ concentration, indicating a potassium conductance change. Serotonin treatment suppressed excitatory amino acid-mediated synaptic potentials (by 48%, Kd = 6.9 microM) and responses to exogenously applied glutamate (70.1 +/- 17% of control, n = 7), but did not alter paired-pulse facilitation, indicating a postsynaptic site of action. Intracellular application of QX-314, a blocker of potassium conductance, significantly reduced depression of synaptic potentials by 5-HT agonists. In cells filled with QX-314, responses to exogenously applied glutamate were not reduced by serotonin or 5-carboxamidotryptamine application. These results indicate that the observed conductance increase associated with 5-HT application accounts for most if not all of the observed depressant effects of 5-HT1A agonists on excitatory amino acid-mediated neurotransmission.
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PMID:5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT1A receptors. 937 96

1. Previous studies have shown that flupirtine, a centrally acting, non-opioid analgesic agent, also exhibits neuroprotective activity in focal cerebral ischaemia in mice and reduces apoptosis induced by NMDA, gp 120 of HIV, prior protein fragment or lead acetate as well as necrosis induced by glutamate or NMDA in cell culture. To study the potential mechanism of the neuroprotective action of flupirtine, we investigated whether flupirtine is able to modulate potassium or NMDA-induced currents in rat cultured hippocampal neurones by use of the whole-cell configuration of the patch-clamp technique. 2. We demonstrated that 1 microM flupirtine activated an inwardly rectifying potassium current (K(ir)) in hippocampal neurones (deltaI=-39+/-18 pA at -130 mV; n=10). This effect was dose-dependent (EC50=0.6 microM). The reversal potential for K(ir) was in agreement with the potassium equilibrium potential predicted from the Nernst equation showing that K(ir) was predominantly carried by K+. Furthermore, the induced current was blocked completely by Ba2+ (1 mM), an effect typical for K(ir). 3. The activation of K(ir) by flupirtine was largely prevented by pretreatment of the cells with pertussis toxin (PTX) indicating the involvement of a PTX-sensitive G-protein in the transduction mechanism (deltaI=-3+/-6 pA at -130 mV; n=8). Inclusion of cyclic AMP in the intracellular solution completely abolished the activation of K(ir) (n=7). 4. The selective alpha2-adrenoceptor antagonist SKF-86466 (10 microM), the selective 5-HT1A antagonist NAN 190 as well as the selective GABA(B) antagonist 2-hydroxysaclofen (10 microM) failed to block the flupirtine effect on the inward rectifier. 5. Flupirtine (1 microM) could not change the current induced by 50 microM NMDA. 6. These results show that in cultured hippocampal neurones flupirtine activates an inwardly rectifying potassium current and that a PTX-sensitive G-protein is involved in the transduction mechanism.
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PMID:Influence of flupirtine on a G-protein coupled inwardly rectifying potassium current in hippocampal neurones. 942 Dec 79

1. The superficial layers II and III of the entorhinal cortex, which form the main cortical input to the hippocampus, receive a large serotonergic projection from the raphe nuclei and express 5-HT receptors at high density. Here, we studied the effects of serotonin on the intrinsic properties and excitatory synaptic transmission of the superficial medial entorhinal cortex. 2. Intracellular and patch clamp recordings revealed that serotonin hyperpolarized only one-third of the cells, approximately, through a potassium conductance via a GTP-dependent process. 3. Serotonin depressed mixed as well as isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid receptor (AMPAR)- and N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCsapproximately 40 % reduction with 1 microM serotonin). 4. The effect of serotonin on EPSPs/EPSCs was similar in whole-cell versus intracellular recordings; it did not require intracellular GTP and was not visible in glutamate applications to excised patches. Miniature EPSCs recorded in the presence of tetrodotoxin and bicuculline were reduced in frequency, but not altered in amplitude. 5. The effects of serotonin on intrinsic properties and EPSPs were partially mimicked by 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and 5-carboxamido-tryptamine maleate (5-CT), and reduced by 5-HT1A receptor antagonists S-(-)-5-fluoro-8-hydroxy-DPAT hydrochloride (S-UH-301), 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) and spiperone. 6. We conclude that serotonin potently suppresses excitatory synaptic transmission via 5-HT1A receptors in layers II and III of the medial entorhinal cortex by a presynaptic mechanism.
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PMID:Serotonin reduces synaptic excitation in the superficial medial entorhinal cortex of the rat via a presynaptic mechanism. 949 Aug 27

Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5'-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT1A receptor. We conclude that corticosteroids alter the 5-HT1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.
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PMID:Corticosteroids alter 5-hydroxytryptamine1A receptor-effector pathway in hippocampal subfield CA3 pyramidal cells. 949 87

Experiments were carried out to determine the effects of altering the serotonin (5-HT) levels in the hypothalamus on thermoregulatory function in unanesthetized restrained rats. Local perfusion of the hypothalamus with dialysis solution containing 5-hydroxytryptophan (a 5-HT precursor), fluoxetine (a 5-HT reuptake inhibitor), or high potassium significantly increased both colonic temperature (Tco) and the extracellular concentrations of 5-HT in the hypothalamus. Reciprocally, both extracellular concentration of 5-HT in the hypothalamus and Tco were decreased with a dialysis solution containing tetrodotoxin (which blocks the voltage-dependent sodium channel), zero calcium concentration, or systemic administration of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT,5-HT1A agonist). Intrahypothalamic administration of 8-OH-DPAT and (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (a 5-HT2 agonist) produced hypothermic and hyperthermic effects, respectively. The results indicate that elevating the 5-HT levels in the hypothalamus activates postsynaptic 5-HT2 receptors and results in hyperthermic effects, whereas stimulation of presynaptic 5-HT1A receptors in the hypothalamus reduces the endogenous 5-HT release and results in hypothermic effects.
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PMID:Changes in extracellular serotonin in rat hypothalamus affect thermoregulatory function. 964 38


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