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)

Dopamine D2-like receptor labeled by [3H]YM-09151-2 in the rat hippocampus proper was examined by in vitro receptor autoradiography. In the dorsal hippocampus, [3H]YM-09151-2 bindings were high in the whole layers of CA1, the stratum pyramidale of CA4 and the stratum molecular of gyrus dentatus, moderate in the stratum oriens of CA3 and hilus of the gyrus dentatus, and low in remaining CA3 and the subiculum. In the ventral hippocampus, the binding densities were high in the stratum oriens and the stratum radiatum of CA1, the stratum pyramidale of CA4, and the stratum moleculare of gyrus dentatus, moderate in the stratum lacnosum moleculare of CA1 and the hilus of the gyrus dentatus. Saturation analysis using hippocampal sections demonstrated that the Kd value was about five times higher than that using striatal sections. The rank order potency of competition on [3H]YM-09151-2 binding by dopaminergic ligands in the hippocampus was YM-09151-2 > (+)-butaclamol > dopamine > sulpiride > SCH-23390; which shows the appropriate dopamine D2-like receptor profile. The hippocampal [3H]YM-09151-2 binding did not represent serotonergic receptors (5-HT1A and 5-HT2) and sigma receptor, since Ki values of ketanserine, serotonin, 8-OH-DPAT and DTG were much lower than D2-like receptor antagonists. These findings suggest tha [3H]YM-09151-2 binds hippocampal D2-like receptor site with different association kinetics of striatal D2-like receptor site, and demonstrates widespread distribution of D2-like receptor in the hippocampus with distinct region-specific profile.
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PMID:Dopamine D2-like receptors labeled by [3H]YM-09151-2 in the rat hippocampus: characterization and autoradiographic distribution. 755 74

The binding characteristics of [3H]WAY-100635 ([O-methyl 3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride), a potent and selective 5-HT1A antagonist radioligand, were examined in the rat brain using in vitro quantitative receptor autoradiography. The regional distribution of specific [3H]WAY-100635 binding sites was heterogeneous and demonstrated a strong correlation with that of [3H]8-OH-DPAT binding. The highest concentrations of [3H]WAY-100635-labelled sites were found in the lateral septal areas, dorsal raphe n., entorhinal cortex and the hippocampal formation (CA1, CA3 and dentate gyrus). Scatchard transformation of saturation isotherms revealed saturable [3H]WAY-100635 binding sites of high-affinity: in the hippocampal formation, Kd was approximately 1 nM and Bmax ranged between 187 and 243 fmol/mg tissue wet weight, in the entorhinal cortex, Kd = 0.44 nM and Bmax = 194 fmol/mg tissue wet weight, and in the rostral portion of the dorsal raphe n., Kd = 0.52 nM and Bmax = 157 fmol/mg tissue wet weight. The affinity of [3H]WAY-100635 for the 5-HT1A binding site tended to be higher in the dorsal raphe n. and entorhinal cortex compared with that of the hippocampal formation. In contrast, the binding affinity of [3H]8-OH-DPAT in the hippocampal formation was between 1.1 and 2.3 nM and the Bmax was 137 to 183 fmoles/mg tissue wet weight; in the entorhinal cortex, Kd = 3.2 nM and Bmax = 141 fmoles/mg tissue wet weight, and in the rostral portion of the dorsal raphe n., Kd = 3.4 nM and Bmax = 163 fmol/mg tissue wet weight.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quantitative autoradiographic characterisation of the binding of [3H]WAY-100635, a selective 5-HT1A receptor antagonist. 760 35

The serotonin-1A agonists buspirone (BU) and ipsapirone (IPSA) have been demonstrated to exert antidepressant and anxiolytic effects. Since some antidepressant drugs and the antiepileptic substance carbamazepine have calcium antagonistic properties, the interaction of BU and IPSA with carbamazepine and the organic calcium channel blocker verapamil was analyzed in the low Mg2+ induced model epilepsy which has been shown to be suppressed specifically by organic calcium antagonists. BU and IPSA reduced the frequency of occurrence of low magnesium induced field potentials in CA1 and CA3 areas of the hippocampus slice preparation (guinea pigs) in a dose dependent manner. The subthreshold concentrations which yielded no effect were 5 mumol/l for BU and IPSA, 10 mumol/l for carbamazepine and 2 mumol/l for verapamil. Combinations of these subthreshold concentrations elicited a reduction in the repetition rate of field potentials. The results indicate that BU and IPSA behave additively with verapamil and carbamazepine, which may be due to a common action on the same subtype of calcium channels. It may be assumed that besides their action on 5-HT1A receptors BU and IPSA may also have calcium antagonistic properties.
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PMID:Effects of the serotonin-1A agonists buspirone and ipsapirone on field potentials in the hippocampus slice: comparison with carbamzepine and verapamil. 761 4

Microiontophoretic applications of 5-HT and of the 5-HT3 agonist 2-methyl-5-HT produced a current-dependent suppression of firing activity of both hippocampal (CA1 and CA3) and cortical neurons in anesthetized rats. Concomitant microiontophoretic applications of the 5-HT3 antagonists BRL 46470A and S-zacopride, as well as their intravenous injection, did not antagonize the inhibitory effect of 5-HT and 2-methyl-5-HT. In contrast, the 5-HT1A antagonist BMY 7378, applied by microiontophoresis or administered intravenously, significantly reduced the inhibitory action of 5-HT and 2-methyl-5-HT. The firing activity of dorsal raphe 5-HT neurons was also reduced by 5-HT, 2-methyl-5-HT and the 5-HT1A agonist 8-OH-DPAT applied by microiontophoresis. While BRL 46470A (0.1 and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5-HT agonists on 5-HT neuronal firing activity, only that of 8-OH-DPAT was attenuated by the 5-HT1A antagonist (+) WAY 100135. R-zacopride significantly reduced the duration of suppression of firing activity of CA3 pyramidal neurons induced by the electrical stimulation of the ascending 5-HT pathway, and this reducing effect was prevented by the three 5-HT3/5-HT4 antagonists renzapride, S-zacopride and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion experiments, both BRL 46470A and S-zacopride antagonized the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [3H]-5-HT in both rat frontal cortex and hippocampus slices. These findings suggest that, in vivo, the suppressant effect of 2-methyl-5-HT on the firing activity of dorsal hippocampus pyramidal, somatosensory cortical, and dorsal raphe 5-HT neurons is not mediated by 5-HT3 receptors, but rather by 5-HT1A receptors. The attenuating effect of R-zacopride on the effectiveness of the stimulation of the ascending 5-HT pathway is not mediated by 5-HT3 receptors. In contrast, in vitro, the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [3H]5-HT in both frontal cortex and hippocampus slices is mediated by 5-HT3 receptors.
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PMID:Pre- and post-synaptic effects of the 5-HT3 agonist 2-methyl-5-HT on the 5-HT system in the rat brain. 762 30

We report two serotonin (5-hydroxytryptamine, 5-HT) receptors, MR22 and REC17, that belong to the G-protein-associated receptor superfamily. MR22 and REC17 are 371 and 357 amino acids long, respectively, as deduced from nucleotide sequence and share 68% mutual amino acid identity and 30-35% identity with known catecholamine and 5-HT receptors. Saturable binding of 125I-labeled (+)-lysergic acid diethylamide to transiently expressed MR22 in COS-M6 cells was inhibited by ergotamine > methiothepin > 5-carboxamidotryptamine > 5-HT. For REC17, the rank of potency was ergotamine > 5-carboxamidotryptamine > methiothepin > methysergide > 5-HT. Both were insensitive to 5-HT1A, 5-HT1D or 5-HT2 serotonergic ligands [8-hydroxy-2-(di-n-propylamino)tetralin, sumatriptan, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The mRNAs encoding MR22 were detected in the CA1 region of hippocampus, the medial habenula, and raphe nuclei. In contrast, mRNAs encoding REC17 were found throughout the rat central nervous system. We propose that REC17 and MR22, designated as 5-HT5 alpha and 5-HT5 beta, represent a distinct subfamily of 5-HT receptors.
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PMID:Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain. 768 2

The novel selective 5-HT1A receptor antagonist radioligand [3H]WAY 100635 ([O-methyl-3H]N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- pyridyl)cyclohexane-carboxamide) was injected i.v. to mice in an attempt to label in vivo central 5-HT1A receptors. Although 5 min after the i.v. injection of [3H]WAY 100635 (4-7.6 muCi per mouse) the amount of tritium found in the whole brain only accounted for 1.5-1.8% of the injected radioactivity, regional differences in 3H accumulation already corresponded to those of 5-HT1A receptor density. Optimal data were obtained 1 h after [3H]WAY 100635 injection as the distribution of 3H in brain was exactly that of 5-HT1A receptor binding sites in mouse brain sections labelled in vitro with [3H]WAY 100635. In particular, high level of labelling was found in the lateral septum, gyrus dentatus and CA1 area of Ammon's horn in the hippocampus, dorsal raphe nucleus and entorhinal cortex. No labelling was found in he substantia nigra, and 3H accumulated in the cerebellum represented only 12-14% of that found in the hippocampus. Pretreatment with various drugs indicated that only 5-HT1A receptor ligands were able to decrease the accumulation of 3H in all the brain areas examined except in the cerebellum. Assuming that only non-specific binding took place in the latter structure, it was possible to calculate the ID50 values of 5-HT1A receptor agonists (8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), S 14506 (1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl+ ++)piperazine) and S 20499 ((+)-4-[N-(5-methoxy-chroman-3-yl)-N-propylamino]butyl-8- azaspiro-(4,5)-decane-7,9-dione)) and antagonists (spiperone, (-)-tertatolol, (+)-WAY 100135 (N-tert-butyl-3,4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl- propanamide)) as inhibitors of 3H accumulation in the hippocampus of [3H]WAY 100635-injected mice. Comparison of these values with the in vitro affinity of the same ligands for hippocampal 5-HT1A receptors revealed marked variations in the capacity of 5-HT1A receptor agonists and antagonists to reach the brain when injected via the subcutaneous route in mice.
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PMID:Selective in vivo labelling of brain 5-HT1A receptors by [3H]WAY 100635 in the mouse. 770 51

Serotonin (5-HT) mediates its effects on neurons in the central nervous system through a number of different receptor types. To gain better insight as to the localization of 5-HT responsive cells, the distribution of cells expressing mRNAs encoding the three 5-HT receptor subtypes 1A, 1C, and 2 was examined in rat brain with in situ hybridization using cRNA probes. 5-HT1A receptor mRNA labeling was most pronounced in the olfactory bulb, anterior hippocampal rudiment, septum, hippocampus (dentate gyrus and layers CA1-3), entorhinal cortex, interpeduncular nucleus, and medullary raphe nuclei. 5-HT1C receptor mRNA labeling was the most abundant and widespread of the three 5-HT receptor subtypes examined. Hybridization signal was densest in the choroid plexus, anterior olfactory nucleus, olfactory tubercle, piriform cortex, septum, subiculum, entorhinal cortex, claustrum, accumbens nucleus, striatum, lateral amygdala, paratenial and paracentral thalamic nuclei, subthalamic nucleus, substantia nigra, and reticular cell groups. 5-HT2 receptor mRNA was localized to the olfactory bulb, anterior hippocampal rudiment, frontal cortex, piriform cortex, entorhinal cortex, claustrum, pontine nuclei, and cranial nerve motor nuclei including the oculomotor, trigeminal motor, facial, dorsal motor nucleus of the vagus, and hypoglossal nuclei. The distributions of mRNAs for the three different 5-HT receptor subtypes overlap with regions that bind various 5-HT receptor-selective ligands and are present in nearly all areas known to receive serotonergic innervation. The results of this study demonstrate that neurons which express these 5-HT receptor subtypes are very widespread in the central nervous system, yet possess unique distributions within the rat brain. Moreover, previously unreported regions of 5-HT receptor subtype expression were observed, particularly with the 5-HT2 receptor riboprobe in the brainstem. Finally, several brain areas contain multiple 5-HT receptor subtype mRNAs, which leads to the possibility that individual cells may express more than one 5-HT receptor subtype.
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PMID:Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain. 770 47

This investigation was performed to determine the ability of serotonin in inhibiting bicuculline-induced epileptiform bursts in brain slices of male Sprague-Dawley rats. In all experiments, intracellular recording techniques were employed on CA1 neurons of the hippocampus. The neurons were stimulated either directly by the recording electrode or indirectly (synaptic stimulation) using a bipolar electrode placed on the CA2/CA3 region. Serotonin (20 microM) inhibited the directly evoked bursts of action potentials and caused a membrane hyperpolarization and decrease in membrane input resistance in untreated CA1 neurons. In the same experiments, serotonin inhibited the synaptically evoked action potential as well. Additionally, serotonin inhibited epileptiform bursts induced by single presynaptic stimuli in the presence of bicuculline. Moreover, in the concomitant presence of serotonin and bicuculline, there was a decrease in the number of spikes in bursts evoked by direct stimulation. Inhibition of epileptiform bursts was also achieved with the selective 5-HT1A agonist 8-hydroxydipropyl-amino-tetralin (8-OH-DPAT). The presence of the 5-HT3 antagonist MDL 72222 (30 microM), and the 5-HT2 antagonist ketanserin (3 microM) did not influence the ability of serotonin to inhibit epileptiform bursts. In the presence of bicuculline, the inhibitory action of serotonin, 8-OH-DPAT or the combination of serotonin, MDL 72222 and ketanserin, was accompanied by a membrane hyperpolarization and a decrease in membrane input resistance. To ascertain if serotonin can be applied on other models of epilepsy, as well, we demonstrate the inhibition of epileptiform activity in the kainic acid treated brain slice preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of epileptiform activity by serotonin in rat CA1 neurons. 771 72

Glucocorticoids and serotonin (5-HT) modulate behaviour and hypothalamic-pituitary-adrenal (HPA) axis responses. The two systems interact prominently in the hippocampus, where these effects may occur. We have previously shown that hippocampal 5-HT2C receptor mRNA expression is increased by adrenalectomy or central 5-HT lesions. We have now determined expression of corticosteroid and 5-HT receptor subtype genes in the hippocampus across the diurnal cycle, when there are changes both in plasma corticosterone and hippocampal 5-HT levels, as well as the responses of these transcripts to acute and chronic stress, using in situ hybridisation histochemistry. Expression of both glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNAs was significantly higher (131-153%) in the hippocampus at 08.00 h (corticosterone nadir) than at 20.00 h (corticosterone peak). 5-HT2C receptor mRNA expression also showed circadian variation (106-184% higher in CA1-CA3 in the morning). Hippocampal 5-HT1A and 5-HT2A receptor mRNA expression had no diurnal variation. Chronic (15 day) adjuvant arthritis stress, abolished the circadian corticosterone nadir, maintaining plasma corticosterone around diurnal peak values. Chronic arthritis stress suppressed hippocampal 5-HT2C receptor mRNA expression at 08.00 h to levels comparable to 20.00 h controls. By contrast to chronic stress, 6 h after acute laparotomy stress, plasma corticosterone was elevated above control (20.00 h) and 5-HT2C receptor mRNA expression was increased (CA2). Neither acute nor chronic stress altered MR, GR, 5-HT1A or 5-HT2A receptor mRNA expression in any hippocampal subfield. These results show that hippocampal expression of the 5-HT2C receptor gene, but not other subtypes, is sensitive to a variety of manipulations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of serotonin and corticosteroid receptor gene expression in the rat hippocampus with circadian rhythm and stress. 772 17

The effect of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, on spatial and non-spatial learning in a water maze was studied using two tasks of equal difficulty, with the same motor, motivational and reinforcement demands. Rats were examined for choice accuracy in a two-platform spatial discrimination task. Rats treated subcutaneously with 100 micrograms/kg 8-OH-DPAT were impaired in choice accuracy with no effect on latency. Treated rats made more errors of omission than controls only on days 1 and 2 of training. Infusion of 1 microgram/microliter spiroxatrine (SPX) or 5 micrograms/microliters of (+)WAY100135, two potent 5-HT1A receptor antagonists, in the CA1 region of the dorsal hippocampus antagonized the impairment in choice accuracy caused by 8-OH-DPAT. The effect on errors of omission on days 1 and 2 of training were not significantly modified by spiroxatrine or (+)WAY100135. Rats treated with 8-OH-DPAT were not impaired in their ability to learn a visual discrimination in a water maze. The results suggest that stimulation of 5-HT1A receptors in the CA1 region of the dorsal hippocampus impairs spatial but not visual discrimination in rats.
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PMID:8-OH-DPAT impairs spatial but not visual learning in a water maze by stimulating 5-HT1A receptors in the hippocampus. 774 2


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