Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 bilateral olfactory bulbectomy on serotonergic 5-HT2 and 5-HT1A receptor binding were studied in the frontal cortex (FC), limbic structures (LS), including the hippocampus, amygdala, olfactory tubercule, and piriform cortex, and hypothalamus (HTH) in mice. Bulbectomy resulted in the increase of Bmax for [3H]spiperone binding with 5-HT2 receptors in FC in C57Bl/6j. The receptors in LS and HTH remained unchanged. Subchronic treatment of the bulbectomized mice with antidepressant trazodone (20 mg/kg/day, IP, 14 days) induced downregulation of 5-HT2 receptors in FC and LS. The other two antidepressants used, amitriptyline (20 mg/kg/day, IP, 14 days) and imipramine (10 mg/kg/day, IP, 14 days), did not alter these receptors. [3H]8-OH-DPAT binding with 5-HT1A receptors was not altered by bulbectomy in any brain area in C57Bl/6j mice. Amitriptyline and trazodone decreased Bmax for these receptors in FC in the bulbectomized mice while imipramine was ineffective. Amitriptyline and imipramine significantly increased Bmax and decreased Kd in HTH, and trazodone displayed the same tendency. Bulbectomy did not alter 5-HT2 receptors in DBA/2j mice. Amitriptyline increased Kd in the all brain areas without changing Bmax in the bulbectomized DBA/2j mice. Trazodone significantly decreased Bmax in FC and increased Kd in FC and LS. Imipramine decreased Bmax while increasing Kd in LS. The possible involvement of the serotonin receptor subtypes in the bulbectomy-induced behavioral deficits and in the restorative action of the antidepressants is discussed.
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PMID:Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice. 851 75

Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of serotonin receptor. The antiemetic effects of LY228729 [(-)-4-(dipropylamine)-1,3,4,5-tetrahydrobenz-(c,d)indole-6- carboxamide], a 5-HT1A receptor agonist, were tested and compared to the antiemetic effects of the 5-HT3 receptor antagonists ondansetron, tropisetron, and MDL 72222 (3-tropanyl-3,5-dichlorobenzoate). The emetic stimuli tested are known to be blocked by 5-HT3 antagonists in species other than the pigeon. In the pigeon, LY228729 totally abolished vomiting induced by fully emetic doses of cisplatin (10 mg/kg), ipecac (3 ml/kg), emetine (10 mg/kg), and a 5-HT3 agonist, m-(chlorophenyl)-biguanide (1.25 mg/kg). MDL 72222 blocked ipecac-induced vomiting in a dose-related manner and was partially effective in attenuating cisplatin-induced emesis. Ondansetron and tropisetron were partially effective in blocking emetine- and mCPBG-induced vomiting. Ondansetron exhibited an intrinsic emetic response that could not be blocked by MDL 7222, but which was eliminated by LY228729. It was concluded that 5-HT1A agonists are more effective in the pigeon than are 5-HT3 antagonists against these types of emetic stimuli. These results broaden the range of emetic stimuli that are blocked by 5-HT1A agonists in the pigeon.
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PMID:Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon. 854 76

The demonstrated efficacy in anxiety disorders of drugs such as buspirone or fluoxetine has emphasized the importance of 5-hydroxytryptamine (5-HT or serotonin). Buspirone is a selective agonist at a subtype of serotonin receptor termed 5-HT1A, whereas fluoxetine is a selective inhibitor of the reuptake of 5-HT. At least 14 types of mammalian serotonin receptors have been isolated and classified into seven major families, using pharmacologic, transductional, and structural criteria. The subtypes of serotonin receptors are localized in different regions of the brain. Selective compounds for particular subtypes of serotonin receptors may yield selective pharmacologic effects. Since the latency between the initiation of treatment with an SSRI and the appearance of clinical effects may be due to the desensitization of presynaptic autoreceptors, the development of drugs to decrease latency is an active area of investigation. This article provides a brief overview of the physiology and pharmacology of serotonin systems so that the relationship between serotonin compounds and anxiety can be better understood.
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PMID:Serotonin receptor specificity in anxiety disorders. 864 98

The present study was designed to determine whether abnormalities in serotonin receptor binding co-exist with the presynaptic serotonergic deficits that have previously been identified in the genetically epilepsy-prone rat (GEPR) brain. In vitro binding of [3H]8-OH-DPAT (0.16-10.3 nM) to 5-HT1A receptor sites was found to be decreased in the hippocampus of severe seizure GEPRs (GEPR-9s) when compared to nonepileptic control rats, while no difference in [3H]8-OH-DPAT binding was observed in the GEPR-9 corpora quadrigemina or midbrain tegmentum. The decreased binding of [3H]8-OH-DPAT to hippocampal membranes was due to a decrease in Bmax (P < 0.001), rather than to a change in the Kd. Conversely, in vitro binding of [125I]cyanopindolol (2-400 pM) to 5-HT1B receptor sites was increased in the GEPR-9 hippocampus, corpora quadrigemina and midbrain tegmentum when compared to nonepileptic control rats. The increased binding of [125I]cyanopindolol in all three regions resulted from an increase in the Bmax (P < 0.05), rather than a change in the Kd. These finding suggest that in addition to the innate reduction in 5-HT presynaptic markers, GEPR-9s also exhibit abnormalities in the density of 5-HT1A and 5-HT1B receptors in some regions of the brain. Inasmuch as serotonin acts to attenuate audiogenic seizures in GEPRs, these abnormalities in 5-HT receptor binding may contribute to the seizure susceptibility exhibited by these animals.
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PMID:Abnormalities in 5-HT1A and 5-HT1B receptor binding in severe-seizure genetically epilepsy-prone rats (GEPR-9s). 868 90

The zwitterionic detergent, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), is mild, non-denaturing, and extensively used for solubilizing membrane proteins and receptors. We report here that the critical micelle concentration (CMC) of CHAPS is dependent on the concentration of NaCl in the solution. Thus, the CMC of CHAPS decreases from 6.41 mM in absence of any salt to 4.10 mM in presence of 1.5 M NaCl. The logarithm of the CMC values appear to have a linear relationship with the salt concentration. Such changes in CMC with ionic strength have important implications in solubilization of membrane-bound neuronal receptors. This is shown by optimal solubilization of the serotonin receptor type 1A (5-HT1A) from bovine brain hippocampal crude (native) membrane by CHAPS at premicellar concentration under high salt conditions.
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PMID:Dependence of critical micelle concentration of a zwitterionic detergent on ionic strength: implications in receptor solubilization. 870 16

Drugs that enhance brain serotonin function (direct agonists, serotonin uptake inhibitors and serotonin releasers) increase serum corticosterone concentration in rats, and in many cases ACTH has been shown to be similarly increased. At least two distinct serotonin receptor subtypes can mediate this effect. One is the 5-HT1A receptor, and the other seems to be a 5-HT2A receptor. Possibly, the 5-HT2C receptor or other receptors can also mediate these effects. The increase in serum corticosterone seems to be one useful marker in characterizing drug effects on serotonergic function. Much needs to be learned about the physiological importance and roles of this serotonergic influence on pituitary-adrenocortical function. Some studies have suggested it may be important in the diurnal rhythmicity of glucocorticoid secretion and perhaps in some stress effects. Serotonergic activation can also increase plasma levels of ACTH and cortisol in humans. Although the effects in humans are less well characterized than in rats, they seem to be useful as a way of probing brain serotonergic function in disease or after drug treatment. As more drugs that act selectively on a single receptor subtype become available for use in humans, more precise information about particular receptor subtypes should be attainable.
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PMID:Serotonin receptors involved in regulation of pituitary-adrenocortical function in rats. 878 5

A strategy is described that exploits allele-specific amplification (ASA-PCR) and electrochemiluminescence (ECL) detection technology to rapidly and cheaply screen large numbers of DNAs arranged in pooled matrices in order to identify individual nucleotide sequence variants. To demonstrate this strategy, a large genomic DNA collection was screened for two nucleotide variants in the 5-HT1A serotonin receptor gene and individual heterozygotes were identified. Conversion of two SSCP variants to allele-specific PCR polymorphisms was accomplished, and PCR product capture and ECL detection were enabled by the covalent addition of biotin to allele-specific PCR primers and ruthenium to the nonspecific PCR primer. A two-level DNA pooling strategy was used to reduce the number of individual PCR reactions required. Pooling experiments established that ASA-PCR with ECL detection is sufficiently sensitive to reproducibly detect a single specific allele in the presence of a 40-fold excess of genomic DNA from individuals negative for the specific allele. The detection sensitivity of the ECL device and the design of the pooled DNA arrays reduced the number of PCRs required to detect the rare individuals with the variant sequences by approximately 90%. This strategy is called mass allele detection (MAD).
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PMID:Mass allele detection (MAD) of rare 5-HT1A structural variants with allele-specific amplification and electrochemiluminescent detection. 882 30

While serotonin has been shown to play an important role in peripheral pain mechanisms, the specific subtypes of receptors involved and their differential distribution between the sensory and sympathetic nervous system remains poorly understood. In this study, the presence of messenger RNA for rat serotonin receptor subtypes in peripheral sensory and sympathetic ganglia was detected using the method of polymerase chain reaction. Lumbar dorsal root ganglia, superior cervical sympathetic ganglia and lumbar sympathetic ganglia were excised from anesthetized Sprague-Dawley rats. Oligonucleotide primers were chosen based on unique regions of complementary DNA sequence for each of the 12 cloned rat serotonin receptor subtypes (i.e. 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5A, 5-HT5B, 5-HT6 and 5-HT7) and high stringency conditions were used during polymerase chain reaction. Within lumbar dorsal root ganglia, the presence of the 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT3 and 5-HT7 receptor subtype messenger RNAs was detected. Within superior cervical ganglia, the presence of messenger RNA for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3, 5-HT6, and 5-HT7 receptor subtypes was detected. Lumbar sympathetic ganglia displayed banding identical to the superior cervical ganglia with the exception of the 5-HT6 receptor which was not detected in the lumbar sympathetic ganglia. The polymerase chain reaction product from each positively-detected receptor subtype was subcloned and sequenced and found to correspond to published complementary DNA sequences. Findings from this study may direct further efforts to determine the role of 5-hydroxytryptamine receptors in the peripheral nervous system.
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PMID:5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: a polymerase chain reaction study. 884 58

Methylenedioxymethamphetamine (MDMA) is a mood-altering, legally restricted drug that has been reported to inhibit glutamate-evoked firing of cells in the nucleus accumbens. This study used extracellular recording combined with microiontophoresis to examine whether the inhibitory effect of MDMA on neuronal firing in the nucleus accumbens is mediated by serotonin and/or dopamine. Serotonin and serotonin agonists with relative selectivity for the receptor subtypes 5-HT1A, 5-HT1B, 5-HT2A/2C and 5-HT3 all significantly (P < 0.01) inhibited glutamate-evoked firing of cells in the nucleus accumbens compared to the effects of an acidic saline control solution (30-60 nA, 60 s ejection currents for all). The current (dose)-dependent inhibition produced by the serotonin agonists did not differ significantly from the inhibition produced by MDMA except for the 5-HT1A agonist 8-hydroxy-(2-di-n-propylamino) tetralin, which inhibited glutamate-evoked firing significantly more than MDMA or any of the other serotonin agonists. At the highest ejection current tested (60 nA, 60 s), glutamate-evoked firing was inhibited by MDMA in 94% of tested cells, by serotonin in 80% of tested cells and by the serotonin receptor subtype agonists in 95-100% of the tested cells. In addition to being mimicked by serotonin and serotonin agonists, MDMA-induced inhibition of glutamate-evoked firing in the nucleus accumbens was partially blocked by the serotonin antagonists ketanserin (100% of tested cells), methysergide (80% of tested cells), methiothepin (100% of tested cells) and WAY100135 (100% of tested cells). Furthermore, application of the serotonin uptake blocker fluoxetine, which prevents MDMA-induced serotonin release, also significantly attenuated MDMA-induced inhibition of glutamate-evoked firing in all of the cells that were tested. These observations suggest that MDMA-induced inhibition of nucleus accumbens cell firing is at least partially mediated by serotonin. Depletion of dopamine by pretreatment with the neurotoxin 6-hydroxydopamine and the synthesis inhibitor alpha-methyl-p-tyrosine blocked the inhibition of glutamate-evoked firing produced by MDMA applied with low ejection currents (30-40 nA, 60 s). However, this dopamine depletion had no effect on inhibition of glutamate-evoked firing produced by serotonin ejected with low or high currents (20-60 nA, 60 s). These results suggest that both dopamine release and an intermediate step of MDMA-induced serotonin release are necessary for the inhibitory effects of MDMA on neuronal excitability in the nucleus accumbens. The dopamine- and serotonin-mediated inhibitory effects of MDMA on glutamate-evoked firing of nucleus accumbens cells may play a role in the mood-altering properties of this increasingly popular drug.
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PMID:Methylenedioxymethamphetamine-induced inhibition of neuronal firing in the nucleus accumbens is mediated by both serotonin and dopamine. 886 98

Electrophysiological studies indicate that certain 5-HT1A receptor antagonists increase the basal firing rate of some but not all raphe neurons by antagonizing the inhibitory endogenous serotonin tone operating on the somatodendritic pulse-modulating presynaptic 5-HT1A autoreceptors. This effect should enhance the synaptic concentration of 5-HT (5-hydroxytryptamine) in serotonergic terminal fields, which may then activate postsynaptic 5-HT receptors. However, in vivo microdialysis studies show that generally such 5-HT1A antagonists by themselves do not increase the basal 5-HT release but potentiate the ability of serotonin reuptake blockers to increase the neuronal serotonin terminal output in the rat brain via the above mechanism. The purpose of the present study was to determine whether antagonism of the proposed endogenous serotonin tone on the 5-HT1A autoreceptors can potentiate the activity of other postsynaptic serotonin receptors. To this end, we utilized the head-twitch response (HTR) in mice as an in vivo model of postsynaptic 5-HT2A receptor function. The selective and silent 5-HT1A receptor antagonist, S-(-)UH 301, by itself, in a dose-dependent manner, produced the HTR in normal but not in reserpinized animals. The 5-HT2A antagonist, SR 46349B, completely prevented S-(-)UH 301-induced HTR. Pretreatment with S-(-)UH 301 also potentiated 5-hydroxytryptophan (5-HTP)-induced HTR both in normal and in the reserpinized mice. At low doses (0.06-0.25 mg/kg), the 5-HT2A selective agonist, 8-OH DPAT, significantly but partially inhibited 5-HTP-induced HTR. However, further attenuation was not observed following the administration of larger doses of 8-OH DPAT. Depending upon the dose used, S-(-)UH 301 pretreatment not only antagonized but also broke through the inhibitory effect of 8-OH DPAT on 5-HTP-induced HTR. The selective (sertraline) and nonselective (cocaine) serotonin reuptake blockers potentiated the ability of 5-HTP to induce the head-twitch behavior in mice. Pretreatment with S-(-)UH 301 enhanced the potentiating effect of serotonin reuptake blockers on the 5-HTP induced HTR. These results suggest that an endogenous 5-HT tone via the discussed mechanism controls the terminal field synapticactivity of serotonergic neurons in mice. In addition, disinhibition of pulse-modulating 5-HT1A autoreceptors by S-(-)UH 301 can potentiate the synaptic effects of serotonin reuptake blockers as well as the serotonin precursor 5-HTP. However, a more firm general conclusion regarding antagonism of presynaptic 5-HT1A receptors leading to indirect functional enhancement of other postsynaptic serotonergic receptors can only be made when the above hypothesis is further tested with other selective 5-HT1A receptor antagonists (such as WAY 100 635), which we were unable to obtain. The present study is the first report to show that a selective 5-HT1A antagonist by itself can produce a serotonin-mediated function via indirect stimulation of another serotonin receptor subtype in mice.
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PMID:The mechanism by which the selective 5-HT1A receptor antagonist S-(-) UH 301 produces head-twitches in mice. 887 31


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