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)

Anti-idiotypic antibodies were generated by immunizing rabbits with affinity-purified antibodies to serotonin (5-hydroxytryptamine; 5-HT). Anti-5-HT activity was removed from the resulting antisera by chromatography through a 5-HT affinity column. The anti-idiotypic antibodies were demonstrated by enzyme-linked immunosorbent assay to bind to affinity-purified whole anti-5-HT antibodies and their Fab fragments. Anti-idiotypic antibodies, purified by affinity chromatography on columns to which antibodies to 5-HT were coupled, competed with 5-HT (covalently bound to protein) for the binding sites on anti-5-HT antibodies and serotonin binding protein. The anti-idiotypic antibodies antagonized the binding of [3H]5-HT to membranes isolated from the cerebral cortex, striatum, and raphe area more than to membranes from hippocampus or cerebellum. The anti-idiotypic antibodies also blocked the binding of the 5-HT1B-selective ligand (-)-[125I]iodocyanopindolol (in the presence of 30 microM isoproterenol) to cortical membranes. In contrast, anti-idiotypic antibodies failed to inhibit binding of the 5-HT1A-selective ligand 8-hydroxy-2-(di-n-[3H]propylamino)-tetralin [( 3H]8-OH-DPAT) to raphe area membranes or hippocampal membranes. These observations suggested that the anti-idiotypic antibodies may recognize some 5-HT receptor subtypes but not others. This hypothesis was tested by ascertaining the ability of anti-idiotypic antibodies to immunostain cells transfected in vitro with cDNA encoding the 5-HT1C or 5-HT2 receptor or with a genomic clone encoding the 5-HT1A receptor. Punctate sites of immunofluorescence were found on the surfaces of fibroblasts that expressed 5-HT1C and 5-HT2 receptors, but not on the surfaces of HeLa cells that expressed 5-HT1A receptors. Immunostaining of cells by the anti-idiotypic antibodies was inhibited by appropriate pharmacological agents: immunostaining of cells expressing 5-HT1C receptors was blocked by mesulergine (but not ketanserin, 8-OH-DPAT, or spiperone), whereas that of cells expressing 5-HT2 receptors was blocked by ketanserin or spiperone (but not mesulergine or 8-OH-DPAT). The anti-idiotypic antibodies failed to inhibit the uptake of [3H]5-HT by serotonergic neurons. It is concluded that the anti-idiotypic antibodies generated with anti-5-HT serum recognize the 5-HT1B, 5-HT1C, and 5-HT2 receptor subtypes; however, neither 5-HT1A receptors nor 5-HT uptake sites appear to react with these antibodies.
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PMID:Identification of serotonin receptors recognized by anti-idiotypic antibodies. 186 Nov 58

The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- 23 fmol/mg protein) sites. In competition experiments, 5-HT and 5-carboxyamidotryptamine (5-CT), as well as ergotamine, lysergic acid, sumatriptan and RU-24969 exhibited high affinity for these sites. This pharmacological profile is concordant with the ligand selectivity pattern reported for 5-HT1D receptors in other species and thus provides further evidence for its existence in human temporal cortex. In addition, the competition profile of some ligands, particularly of unlabelled 5-HT, 5-CT and ergotamine, revealed the existence of a lower affinity binding site. The latter suggests receptor heterogeneity or the presence of a lower affinity state of 5-HT1D receptors.
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PMID:Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex. 191 37

1. 1-3(Chlorophenyl)piperazine (mCPP) (5 mg kg-1, i.p.) inhibited 2 h food intake in rats previously deprived of food for one day. Ten 5-hydroxytryptamine (5-HT) antagonists given s.c. opposed this hypophagic response. Calculated ID50 values correlated significantly with reported affinities (r = 0.81, n = 10, P less than 0.01) for 5-HT1C but not for 5-HT2, 5-HT1A, 5-HT1B or 5-HT1D receptors. 2. ID50 values of the ten antagonists against 5-hydroxytryptophan (5-HTP) + carbidopa-induced head shakes (a 5-HT2-mediated response) correlated significantly (r = 0.81, n = 10, P less than 0.01) with their affinities for 5-HT2 but not for 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D receptors. 3. ID50 values for inhibition of hypophagia and head shakes did not correlate significantly with each other. 4. Ratios of ID50 values against hypophagia and 5-HT2-mediated head shakes gave indices of relative in vivo potencies independent of differences in drug metabolism and disposition. These ratios correlated highly significantly (r = 0.91, n = 10, P less than 0.001) with the ratios of the affinities of the drugs for 5-HT1C (but not for 5-HT1A, 5-HT1B or 5-HT1B or 5-HT1D receptors) and with their affinities for 5-HT2 receptors. These results strongly support the hypothesis that mediation of mCPP-induced hypophagia is by stimulation of 5-HT1C receptors and the mediation of 5-HTP-induced head twitches by 5-HT2 receptors.
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PMID:Potencies of antagonists indicate that 5-HT1C receptors mediate 1-3(chlorophenyl)piperazine-induced hypophagia. 191 90

We describe here the synthesis of a new serotonin conjugate, S-CM-GTNH2, and its radioiodinated derivative. Quantitative autoradiographic studies on rat and guinea pig brain sections incubated with 2 nM [3H]5-HT showed a preferential affinity of S-CM-GTNH2 for 5-HT1B and 5-HT1D sites. Autoradiograms from brain sections incubated with 0.02 nM S-CM-G[125I]TNH2 showed a heterogeneous anatomical distribution of the labelling with high densities in regions rich in 5-HT1B or 5-HT1D binding sites, and with no labelling of those rich in 5-HT1A or 5-HT1C sites. The pharmacological profiles of the binding sites corresponded to those of 5-HT1B and 5-HT1D receptor subtypes. The radioligand S-CM-G[125I]TNH2 is a good probe for the study of these sites and will be used for their subcellular localization in electron microscopy.
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PMID:[Synthesis and pharmacological study of radioiodinated serotonin derivative specific of 5-HT1B and 5-HT1D binding sites of the central nervous system]. 191 39

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of in utero ethanol exposure on the developing serotonergic system. 192 43

Different serotonin (5-HT) receptor agonists were tested on the electrically stimulated flexor reflex in pithed rats. The 5-HT2 receptor agonist, (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) [+/-)DOI), the mixed 5-HT1/5-HT2 receptor agonist, quipazine, and the 5-HT precursor, l-5-HTP, showed agonistic activity upon intravenous injection while 5-HT was without effect. A combination of the peripheral decarboxylase inhibitor, Ro 4-4602 (benzerazide), the specific 5-HT-uptake inhibitor, citalopram, and l-5-HTP induced a prolonged (greater than 3 h) increase of the flexor reflex in pithed rats. Different compounds were tested for an inhibitory effect against this l-5-HTP-induced flexor reflex. The 5-HT2 antagonists (ketanserin, methergoline and methiothepin) were potent antagonists. (-)Alprenolol (5-HT1A and 5-HT1B receptor antagonist) and the 5-HT3-receptor antagonist, ICS 205-930, were without an antagonistic effect. The inhibitory potencies in the reflex model (l-5-HTP, citalopram and Ro 4-4602) were significantly correlated (r = 0.83, P less than 0.01, r2 = 0.69) with the potencies to inhibit l-5-HTP-induced head twitches and quipazine-induced head twitches (r = 0.81, P less than 0.01, r2 = 0.66). There was less correlation (r = 0.75, P less than 0.01, r2 = 0.56) with the affinities for 5-HT2 receptors in vitro. There was no significant correlation between inhibitory potencies in the reflex model and affinities for dopamine (DA) D-2 receptors or alpha 1-adrenoceptors (r2 = 0.13 and 0.14, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-5-HTP facilitates the electrically stimulated flexor reflex in pithed rats: evidence for 5-HT2-receptor mediation. 196 46

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.
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PMID:Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. 196 70

The effect of 5-HT1A agonists was studied in the isolation-induced social behavioural deficit test. The drugs 8-OH-DPAT (0.125 mg/kg), buspirone (16 mg/kg) and ipsapirone (8 mg/kg) further increased the deficit. Unlike 8-OH-DPAT, the other two drugs may act non-specifically since they reduced spontaneous motor activity at 16 mg/kg, as measured in an activity meter. In addition, 8-OH-DPAT (0.25 mg/kg), buspirone (8 mg/kg) and ipsapirone (8 mg/kg) decreased exploratory activity in the open-field test. Since the smallest active doses were very close in the behavioural deficit and in the open-field tests, it is suggested that a common phenomenon, increased emotionality or reactivity, sustained both these reductions in activity. The increase in the behavioural deficit induced by 8-OH-DPAT, was likely to have resulted from stimulation of 5-HT1A receptors, since it was impaired by pretreatment with penbutolol, a beta-adrenergic-blocking drug, also known to bind to 5-HT1 receptors. Since it was previously shown that the behavioural deficit was reduced by agonists at 5-HT1B receptors, it is proposed that the behavioural inhibition, resulting from an isolation-induced increase in reactivity is bi-directionally modulated by serotonergic drugs, where 5-HT1A agonists increase and 5-HT1B agonists decrease this inhibition.
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PMID:Increase in the isolation-induced social behavioural deficit by agonists at 5-HT1A receptors. 197 Apr 24

The interactions of tandospirone (formerly called SM-3997) with 5-HT and other neurotransmitter receptor binding sites were determined in brain homogenates. Tandospirone is most potent at the 5-HT1A receptor, displaying a Ki value of 27 +/- 5 nM. The agent is approximately two to three orders of magnitude less potent at 5-HT2, 5-HT1C, alpha 1-adrenergic, alpha 2-adrenergic, and dopamine D1 and D2 receptors (Ki values ranging from 1300 to 41000 nM). Tandospirone is essentially inactive at 5-HT1B receptors; 5-HT uptake sites; beta-adrenergic, muscarinic cholinergic, and benzodiazepine receptors. This pharmacological profile differs slightly from that of other novel anxiolytics such as buspirone, ipsapirone, and gepirone. Saturation and competition studies using 3H-tandospirone also suggest that the drug interacts with 5-HT1A receptor binding sites in rat cortical membranes (KD = 4.5 +/- 0.8 nM; Bmax = 2.2 +/- 0.6 pmol/g tissue). Based on adenylate cyclase studies which measure 5-HT1A receptor-mediated effects, tandospirone displays approximately 60% of the agonist effect of 8-OH-DPAT, a selective 5-HT1A agonist. Thus, the primary pharmacological effect of tandospirone appears to be partial agonism at the 5-HT1A receptor, an activity similar to other pyrimidinyl-piperazines which are being developed as novel anxiolytic agents.
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PMID:Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites. 197 52

This study examined the abilities of 5-hydroxytryptamine (5-HT) agonists with varying selectivity for different subtypes of 5-HT receptors to produce antidepressant-like behavioral effects in the forced swim test in rats. The 5-HT1A agonists 8-OH-DPAT (0.125-1.0 mg/kg, SC) and tandospirone (SM-3997) (5-20 mg/kg, SC) both produced dose-related decreases in immobility time following subchronic treatment in rats. These effects were similar to those of the tricyclic antidepressants imipramine (5-15 mg/kg) and desipramine (5-15 mg/kg). In addition, the 5-HT1A agonists, buspirone (20 mg/kg), gepirone (20 mg/kg) and ipsapirone (10 and 20 mg/kg) demonstrated antidepressant-like effects. Other groups of rats treated subchronically with each of the 5-HT1A agonists or antidepressants showed no increase in locomotor activity, so that general changes in activity could not account for the reduction of immobility time in the forced swim test. 5-HT agonists selective for other receptor subtypes, such as the 5-HT1B/1C agonist m-CPP (5 mg/kg) and the 5-HT2/1C agonist DOB (1 mg/kg), were not effective in this behavioral test. The benzodiazepine diazepam (5 mg/kg) also failed to reduce immobility time, suggesting that anxiolytic properties of 5-HT1A agonists did not mediate this behavioral effect. A common metabolite of some of the 5-HT1A agonists, 1-PP, was ineffective in reducing immobility time. The stimulant d-amphetamine (2 mg/kg) significantly reduced immobility time but also significantly increased locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test. 197 7


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