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

The synthesis of some o-methoxyphenylpiperazines with a benzamide moiety on N-4 alkyl chain was accomplished and their affinity for dopamine and serotonin receptor subtypes was assayed by in vitro receptor binding. The results show that several derivatives had a good affinity both on D-2 and 5-HT1A receptors, the IC50s ranging from 10(-7) to 10(-8) M.
 ...
PMID:5-HT1A and D-2 receptor affinity of o-methoxyphenylpiperazine derivatives with terminal benzamide fragment on N-4 alkyl chain. 2. 766 88

We have used the polymerase chain reaction technique to selectively amplify a guanine nucleotide-binding protein-coupled receptor cDNA sequence from rat striatal mRNA that exhibits high homology to previously cloned serotonin receptors. Sequencing of a full length clone isolated from a rat striatal cDNA library revealed an open reading frame of 1311 base pairs, encoding a 437-residue protein with seven hydrophobic regions. Within these hydrophobic regions, this receptor was found to be 41-36% identical to the following serotonin [5-hydroxytryptamine (5-HT)] receptors: 5-HT2 > 5-HT1D > 5-HT1C > 5-HT1B > 5-HT1A > 5-HT1E. Northern blots revealed a approximately 4.2-kilobase transcript localized in various brain regions, with the following rank order of abundance: striatum >> olfactory tubercle > cerebral cortex > hippocampus. Expression of this clone in COS-7 cells resulted in the appearance of high affinity, saturable binding of (+)-[2-125I] iodolysergic acid diethylamide ([125I]LSD) with a Kd of 1.26 nM. Among endogenous biogenic amines, only 5-HT completely inhibited [125I]LSD binding (Ki = 150 nM). The inhibition of [125I]LSD binding by other serotonergic agonists and antagonists revealed a pharmacological profile that does not correlate with that of any previously described serotonin receptor subtype. In addition, this receptor exhibits high affinity for a number of tricyclic antipsychotic and antidepressant drugs, including clozapine, amoxipine, and amitriptyline. In HEK-293 cells stably transfected with this receptor, serotonin elicits a potent stimulation of adenylyl cyclase activity, which is blocked by antipsychotic and antidepressant drugs. The distinct structural and pharmacological properties of this receptor site indicate that it represents a completely novel subtype of serotonin receptor. Based on its affinity for tricyclic psychotropic drugs and its localization to limbic and cortical regions of the brain, it is likely that this receptor may play a role in several neuropsychiatric disorders that involve serotonergic systems.
 ...
PMID:Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. 768 Jul 51

Ditolyguanidine (DTG) induced a dose-dependent emetic response in pigeons, with 100% of the birds vomiting after 5.6 mg/kg. Retching and vomiting originally induced by DTG could be conditioned to the test situation. Both the unconditioned and conditioned emetic responses were dose-dependently blocked by 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT) and LY228729, agonists at the 5-HT1A subtype of serotonin receptor, but not by the 5-HT3, antagonist tropisetron. Higher doses (0.25-0.5 mg/kg) of tropisetron exhibited intrinsic emetic activity which could also be prevented by 8-OH-DPAT. NAN-190, a putative 5-HT1A partial agonist, produced both an antiemetic response when administered before DTG and also attenuated the antiemetic effects of 8-OH-DPAT. Pentobarbital blocked the conditioned, but not the unconditioned DTG-induced emesis. These results support the possibility that 5-HT1A agonists exhibit antiemetic activity against a broad range of emetic stimuli, including conditioned vomiting which is usually resistant to pharmacological attenuation.
 ...
PMID:Antiemetic effects of 5-HT1A agonists in the pigeon. 782 54

Biochemical and electrophysiological approaches were used to assess the possible changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat brain after a long-term treatment with cericlamine [2-(3,4-dichlorobenzyl)-2-dimethylamino-1-propanol], a novel serotonin reuptake inhibitor with antidepressant properties. Possible changes in other serotonin receptor binding sites (5-HT2A, 5-HT2C and 5-HT3) were also investigated after this treatment. Cericlamine was injected for 2 weeks at a dose (16 mg/kg i.p., twice daily) that ensured complete prevention of 4-methyl-alpha-ethyl-meta-tyramine-induced depletion of brain serotonin. In vitro binding and quantitative autoradiographic studies showed that neither 5-HT1A, 5-HT2A, 5-HT2C nor 5-HT3 receptor binding sites in various brain areas were affected by the 14-day treatment with cericlamine. Although forskolin-stimulated adenylate cyclase activity was significantly increased in hippocampal homogenates from cericlamine-treated rats, the reduction in this enzymatic activity due to 5-HT1A receptor stimulation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was unchanged in these animals as compared with controls. In contrast, in vitro and in vivo electrophysiological recordings of serotoninergic neurons in the dorsal raphe nucleus revealed a clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus the potency of 8-OH-DPAT and ipsapirone to depress the firing rate of these neurons in brain stem slices was significantly reduced after the 2-week treatment with cericlamine. In vivo, the potency of an injection of cericlamine to inhibit the discharge of serotoninergic neurons was also markedly less in rats that had been pretreated for 2 weeks with this drug as compared with controls. However, the inhibitory effects of systemically injected 8-OH-DPAT and ipsapirone on the electrical activity of serotoninergic neurons were as pronounced in cericlamine-treated rats as in controls. In addition, the reduction in serotonin synthesis due to an acute treatment with 8-OH-DPAT (0.1 or 0.3 mg/kg s.c.) was not significantly different in both groups of rats. These data support the idea that postsynaptic (in the hippocampus) and somatodendritic (in the dorsal raphe nucleus) 5-HT1A receptors are differently regulated in the rat brain, because only the latter receptors desensitized after a long-term blockade of serotonin reuptake by cericlamine. They also suggest that the inhibitory influence of systemically administered direct 5-HT1A agonists such as 8-OH-DPAT and ipsapirone on the electrical and metabolic activity of serotoninergic neurons does not result solely from the stimulation of somatodendritic 5-HT1A autoreceptors.
 ...
PMID:Central pre- and postsynaptic 5-HT1A receptors in rats treated chronically with a novel antidepressant, cericlamine. 813 56

A series of cis- and trans-fused hexahydroindeno[2,1-c]pyridines have been prepared and evaluated for affinity and selectivity at the 5-HT1A subtype of the serotonin receptor. Using molecular modeling studies we predicted that the 5-methoxy-trans-fused members of this class would exhibit affinity for this site. In agreement with these predictions, trans-5-methoxy-N-propyl-2,3,4,4a,9,-9a-hexahydro-1H-indeno[2,1-c]pyridi ne (6a) demonstrated moderate affinity and high selectivity for the 5-HT1A binding site, whereas the cis-fused isomer 5a demonstrated virtually no affinity at this site. Additional trans-fused analogs from this series, where the nitrogen was substituted with a variety of alkylene imide containing appendages, demonstrated high (0.60-51 nM) affinity and excellent selectivity for the 5-HT1A site. Certain of these analogs, independent of ring-fusion stereochemistry, also demonstrated high affinity for the 5-HT2 binding site.
 ...
PMID:Synthesis and structure activity relationships of cis- and trans-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-c]pyridines for 5-HT receptor subtypes. 828 83

Agonists for GTP-binding protein (G protein)-coupled receptors are thought to bind with high affinity to the complex of receptor and G protein. Nonhydrolyzable GTP analogs have been shown to disrupt this complex and reduce the binding affinity for many agonists. Antagonists are thought to bind to the receptor whether or not it is coupled to the G protein, and therefore binding remains unchanged in the presence of GTP analogs. The binding of the serotonin 5-hydroxytryptamine (5-HT)2 receptor agonists serotonin (5-HT) and 4-bromo-2,5-dimethoxyphenylisopropylamine is not affected by the presence of GTP analogs when the cloned 5-HT2 receptor is expressed in the 293 human embryonic kidney cell line. The same receptor expressed in mouse NIH3T3 cells is partially sensitive to GTP analogs. Both cell lines have similar proportions of agonist and antagonist binding sites, and agonist stimulation of both cell lines leads to a robust increase in phosphoinositide hydrolysis. Differences in GTP metabolism in 293 cells is not likely to be the cause of the observed difference in inhibition of agonist binding, because the cloned 5-HT1A serotonin receptor expressed in these cells is sensitive to GTP analogs. The GTP-insensitive agonist binding is best explained by the existence of a G protein-receptor complex in 293 cells that is not sensitive to GTP analogs. Such a G protein-receptor complex may explain the fraction of agonist binding in the brain that is not sensitive to GTP analogs.
 ...
PMID:High affinity agonist binding to cloned 5-hydroxytryptamine2 receptors is not sensitive to GTP analogs. 831 23

Alterations in density of some serotonin receptor sites (5-HT1A receptors, 5-HT2 receptors and 5-HT uptake sites) have been reported in postmortem studies of brain obtained from subjects with schizophrenia, suggesting a disturbance in serotonergic transmission in schizophrenia. The purpose of the present study is to investigate [3H]-LY278584 binding to serotonin 5-HT3 receptors in postmortem samples of amygdala from schizophrenic and matched control subjects. As all of the schizophrenic patients but none of the controls had been treated with neuroleptics, we first investigated in rodents the effects of short-term and long-term haloperidol administration on limbic 5-HT3 receptors, and we found no effects. No differences in the maximum number of 5-HT3 binding sites (Bmax) or equilibrium dissociation constant (Kd) between schizophrenics and controls were found in amygdala. This study does not support the presence of an alteration of 5-HT3 receptors in amygdala in schizophrenic patients.
 ...
PMID:Serotonin 5-HT3 receptors in schizophrenia: a postmortem study of the amygdala. 835 29

The interactions between 14 days of repeated restraint stress and daily administration of imipramine or tianeptine (2 h before the beginning of stress) were investigated in rats to assess responses of 5-HT2 and 5-HT1A receptors and serotonin transporter sites labelled by [3H]paroxetine in the cerebral cortex and hippocampus, two brain regions in which adrenal steroid effects on serotonin receptor-binding have been reported. 5-HT2 sites, labelled by [125I]7-amino-8-iodo ketanserin, were decreased in parietal cerebral cortex layers 3 and 5 by imipramine treatment, but not by tianeptine treatment and not by daily restraint stress. Stress, but not antidepressant, depressed 5-HT1A sites labelled with [3H]8-hydroxy-DPAT in hippocampal fields CA3, CA4 and dentate gyrus. [3H]paroxetine-binding to serotonin transporter sites was decreased by tianeptine treatment as well as by imipramine in both hippocampus and cerebral cortex, with some overlap of the fields that were significantly affected, whereas there were no effects of stress per se and no evidence of a stress x drug interaction. These results are discussed in relation to similarities and differences in the effects of different antidepressant drugs on the serotonergic system of the rat brain. Whereas the actions of imipramine and tianeptine on 5-HT2 and 5-HT1A receptors are specific to each drug, the surprising finding of a similar effect of both drugs to reduce serotonin transporter sites labelled by [3H]paroxetine suggest the possibility of a common action for these two drugs in spite of their opposite effects on serotonin re-uptake.
 ...
PMID:Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. 836 29

In order to examine whether cocaine-induced behavioral sensitization is modulated by changes in serotonin receptor subtypes, we measured the binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and of [3H]-ketanserin to 5-HT2 receptors in various brain regions of cocaine-treated and saline-treated (control) rats. As previously reported, repeated administration of cocaine resulted in behavioral sensitization. Stereotypic scores with the cocaine challenge were significantly (P < 0.05) higher in cocaine-pretreated animals than in the saline-pretreated group. Neither acute nor chronic cocaine administration significantly altered the number (Bmax) or the affinity (KD) of either [3H]8-OH-DPAT or [3H]ketanserin binding sites in any of the brain regions examined. These results suggest that the enhanced functional sensitivity of 5-HT1A or 5-HT2 receptor subtypes seen with cocaine may be associated with alterations in processes distal to receptors rather than changes in the number or the affinity of the receptors.
 ...
PMID:Repeated cocaine administration does not affect 5-HT receptor subtypes (5-HT1A, 5-HT2) in several rat brain regions. 840 13

Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells. [125I]DOI ((+/- )-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane), a 5-HT2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT1 and 5-HT3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT1A and 5-HT1C receptors were not detectable. Moreover, RT-PCR indicated that 5-HT2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT2 receptor-mediated response. In addition, a number of selective 5-HT2 receptor agonists (quipazine, alpha-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT1 and 5-HT3 receptor subtypes had little effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor. 847 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>