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)

Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity.
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PMID:[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats]. 127 10

The pharmacological profile of DV-7028, a pyrido triazine derivative, showed that it is a potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonist. DV-7028 bound to 5-HT2 receptors in rat brain membranes with a Ki value of 22 nM and caused shifts to the right of the concentration-contraction curves to 5-HT in rat thoracic aorta and canine femoral arteries, which are attributed to activation of 5-HT2 receptors. The compound was highly active by oral administration (0.1-10 mg/kg) based on blockade of the 5-HT-induced pressor responses in pithed rats. In contrast, DV-7028 had no affinity for 5-HT1A, 5-HT1B and 5-HT1D receptors. The affinity of the compound was 14-26 times greater for the 5-HT2 receptors when compared to 5-HT1C, adrenergic alpha 1, dopamine D2 and histamine H1 receptors. In human platelets, DV-7028 attenuated the aggregation induced by collagen and inhibited the amplifying effect of 5-HT with collagen on platelet aggregation. Furthermore, a 10-day toxicity study revealed that DV-7028 was a safe compound which did not produce lethality at repeated oral doses of 800 mg/kg/day in rats. These results indicate that DV-7028 is a selective and potent 5-HT2 receptor antagonist which is orally active and safe.
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PMID:Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV-7028. 128 70

In cerebral cortex and lateral septal nuclei different serotonergic receptor subtypes coexist, thus a different action on neuronal firing may be expected depending on the receptor activated. Dorsal raphe nucleus stimulation produced an increased rate of firing in cortical layer V, and in lateral septal nuclei. However, firing rate in cortical layer VI remained unchanged after stimulating the dorsal raphe nucleus. Clomipramine is a tricyclic which exerts its main actions on serotonergic receptors, and long-term treatment with this antidepressant produced a selective increased firing rate in lateral septal neurons, but not in cortical neurons. From an electrophysiological point of view, it is concluded that the excitatory actions on firing rate elicited by dorsal raphe nucleus stimulation or clomipramine treatment are mediated by 5-HT2 receptor subtype activation which is likely to be acting as a 5-HT1A modulator in such places where both receptor subtypes coexist.
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PMID:Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. 129 70

The synthesis and the 5-HT1A and 5-HT2 receptor affinity of 2-substituted 1-[3-(4-aryl-1-piperazinyl)propyl]-imidazoles (1-8) has been described. It has been shown that both the N-3 imidazole atom and the N-1 piperazine one should be considered as possible protonation centers under physiological conditions. It has been found that the folded conformations of 1-8 exist predominantly in solution. Moreover, three different modes of interaction of the analyzed compounds with 5-HT1A and 5-HT2 receptor sites have been proposed.
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PMID:Structure-activity relationship studies of CNS agents. Part VII. The effect of the imidazole fragment in 2-substituted 1-[3-(4-aryl-1-piperazinyl)propyl]imidazoles on their interaction modes with 5-HT1A and 5-HT2 receptors. 129 15

The effects of levoprotiline (LEV), a (-)-enantiomer of oxaprotiline (OXA) and a clinically effective antidepressant, on the binding parameters of hippocampal 5-HT1A and cortical 5-HT2 receptors of rats were compared with those of (+)-enantiomer of OXA ((+)-OXA), imipramine and mianserin. Both LEV and (+)-OXA displayed in vitro some affinity for 5-HT1A receptors labelled with [3H]-8-OH-DPAT, and for 5-HT2 receptors labelled with [3H]-ketanserin. Repeated administration of LEV, for 14 days led to a marked increase in the number of 5-HT1A binding sites in the rat hippocampus, with no change in the KD values. (+)-OXA, imipramine and mianserin produced similar effects on 5-HT1A binding parameters. The number of 5-HT2 receptors was increased after two weeks of LEV administration, not altered after (+)-OXA, and decreased after imipramine or mianserin. The number of [3H]-ketanserin binding sites was decreased after four weeks of (+)-OXA administration, but not altered after LEV. The specific binding of [3H]-ketanserin in the rat cerebral cortex was decreased after repeated treatment with LEV and (+)-OXA (ex vivo). In competition studies the affinity of serotonin for [3H]-ketanserin binding sites was decreased in LEV- and increased in (+)-OXA-treated rats. The results suggest that LEV similarly to other antidepressants increases the number of 5-HT1A receptors, however without common alteration in 5-HT2 receptor number and function.
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PMID:Changes in the rat brain 5-HT1A and 5-HT2 receptors after chronic administration of levoprotiline, (+)-oxaprotiline and other antidepressant drugs. 130 56

The effect of a steric hindrance around the protonation center of the model 4-substituted 1-(3-chlorophenyl)-piperazines 1-9 and 11-14 on their affinity for 5-HT1A and 5-HT2 receptor sites was investigated. Additional evidence for hydrophobic interactions between the N-4 hydrocarbon substituents and 5-HT1A receptors has been presented. However, the hydrophobic forces play a minor role in stabilization of the bioactive complex with 5-HT2 receptors. It has also been found that even bulky substituents around the protonation center of 1-aryl-piperazines are well tolerated at both 5-HT1A and 5-HT2 sites.
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PMID:Structure-activity relationship studies of CNS agents. Part VIII. Bulk tolerance around the protonation center of 4-substituted 1-(3-chlorophenyl)piperazines at 5-HT1A and 5-HT2 receptors. 130 59

The family of serotonin receptors consists of at least eight distinct subtypes, divided into four classes based on their pharmacological and functional characteristics. Here we report the cloning and expression in Swiss 3T3 cells of the human 5-HT2 and 5-HT1A receptor subtypes. Both genes encode functional receptors for 5-HT, that differ considerably in genomic structure, primary amino acid sequence, pharmacology and signal transduction. The 5-HT1A receptor transfectants displayed a single high affinity site for the agonist [3H](+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr ([3H]8-OH-DPAT) and a pharmacological profile specific for the 5-HT1A receptor. In these transfectants, 5-HT mediated a dose-dependent inhibition of forskolin-stimulated cAMP levels. Cells expressing the 5-HT2 receptor exhibited high affinity binding for the antagonist [3H]ketanserin with a 5-HT2 receptor specific pharmacological profile. In these cells 5-HT activated phospholipase C in a dose-dependent manner. The 5-HT2 receptor displayed a genomic organization quite different from the 5-HT1A, 5-HT1B and 5-HT1D receptor subtypes. While these receptors are encoded by one single exon, the 5-HT2 receptor is encoded by three exons separated by two introns. The latter finding adds and additional molecular criterion for receptor classification.
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PMID:Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. 133 Jun 47

The activity of central serotonin (5-hydroxytryptamine, 5-HT) systems has been reported to be affected by repeated, and to a lesser extent by acute, lithium chloride (LiCl) treatment. Because (1) acute LiCl administration increases sympathoadrenal function, and in turn plasma glucose levels, and (2) stimulation of either the 5-HT1A, the 5-HT1C or the 5-HT2 receptor subtype has adrenal catecholamine-releasing and hyperglycemic effects, we have investigated the influence of prior blockade of either of these receptor subtypes on plasma catecholamine and glucose responses to acute LiCl administration in conscious, catheterized rats. Acute administration of LiCl (1-8 mEq/kg IV) triggered dose-dependent increases in plasma epinephrine (Epi), norepinephrine (NE), and glucose levels throughout the 60-min analysis. In contrast, administration of NaCl (8 mEq/kg IV) did not alter plasma Epi or NE levels, nor did it affect plasma glucose levels. Prior blockade of 5-HT1A receptor and beta-adrenoceptors by means of (-)-propranolol (5 mg/kg IV), 10 min beforehand) did not affect plasma Epi and NE responses to LiCl (4 mEq/kg), but it did prevent the hyperglycemic effect of LiCl. Plasma Epi, NE and glucose responses to LiCl remained intact in rats pretreated with the 5-HT1C/5-HT2 receptor antagonist LY 53857 (1 mg/kg IV), 10 min beforehand). These results strongly suggest that LiCl-induced adrenal catecholamine release (and hyperglycemia) is not mediated by increased 5-HT release.
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PMID:Serotonin does not mediate the adrenal catecholamine-releasing effect of acute lithium administration in rats. 133 98

The anticonflict activity of m-CPP, a non-selective agonist of 5-HT receptors, was studied in the drinking conflict test in rats. m-CPP administered in doses of 0.125-0.5 mg/kg increased the number of punished licks, the maximum effect having been observed after a dose of 0.25 mg/kg. The anticonflict effect of m-CPP (0.25 mg/kg) was antagonized by the non-selective 5-HT antagonist metergoline (1-4 mg/kg) and by the beta-adrenoceptor blocker SDZ 21009 (2 and 4 mg/kg) with affinity for 5-HT1A and 5-HT1B receptors. On the other hand, the 5-HT1A receptor antagonist NAN-190 (0.5 and 1 mg/kg), the 5-HT2 receptor antagonist ritanserin (0.25 and 0.5 mg/kg), and the beta-blockers betaxolol (8 mg/kg) and ICI 118,551 (8 mg/kg) with no affinity for 5-HT receptors did not affect the effect of m-CPP. The effect of m-CPP was not modified, either, in animals with the 5-HT lesion produced by p-chloroamphetamine. These results suggest that the anticonflict effect of m-CPP described above results from stimulation of 5-HT1B receptors--most probably these which are located postsynaptically.
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PMID:Involvement of 5-HT1B receptors in the anticonflict effect of m-CPP in rats. 134 21

Some substituted 3-phenylmorpholines (10a-e,j,k) and 3-thienylmorpholines (10f,g), isosteres of 3-(3-hydroxy-phenyl)-N-n-propylpiperidine (3-PPP), were prepared and submitted to binding assays on D-2 dopaminergic and 5-HT1 and 5-HT2 serotonergic receptors, in comparison with 3-PPP and its analogue 3a,b. The results show the loss of D-2 affinity for all morpholines, while a certain activity was still observable for piperidine derivatives. Regarding the serotonergic affinity, only chloro and methoxy derivatives (10a-d) were moderately active on the 5-HT1A receptor, either when the substituent was in the C-2 or C-3 position, whereas no tested compounds showed affinity toward the 5-HT2 receptor.
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PMID:Oxygen isosteric derivatives of 3-(3-hydroxyphenyl)-N-n-propylpiperidine. 135 63


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