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 binding profile of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([3H]8-OH-DPAT) to serotonin1A (5-HT1A) sites in rat hippocampal, frontocortical and striatal membranes has been compared. In these regions, [3H]8-OH-DPAT labels both a high and a low-affinity binding site; the affinity values for each of the two sites are comparable in the different brain regions, but have different maximal capacity. By modifying the experimental conditions in a series of hippocampal membrane preparations, reciprocal changes in the proportion of the two sites were observed suggesting that they represent, at least in this region, different conformations or affinity states of a single receptor protein. In contrast to the lower affinity state, it appears that the high-affinity state is stabilized by coupling with a G-protein. Evidence supporting this statement is provided by addition of the guanine nucleotide Gpp(NH)p, breakage of labile disulfide bonds using N-ethylmaleimide and increasing membrane rigidity with ascorbate-induced lipid peroxidation, conditions which all reduced the density of receptors in the high-affinity state. Moreover, the high-affinity state appears to be stabilized at the expense of the lower affinity state in the presence of Mn2+. On the other hand, a complete shift to the low-affinity binding state was observed after a 24 h in vivo treatment with inhibitors of monoamine oxidase A (phenelzine or clorgyline) but not of monoamine oxidase B (deprenyl). This disappearance of the high-affinity state with a concomitant increase in the binding capacity of the low-affinity state was reproduced by inhibiting monoamine oxidase A in vitro, as well as by reducing preincubation washout periods. Also, competitors of the [3H]8-OH-DPAT binding site, such as serotonin and unlabelled 8-OH-DPAT, display two affinity states while others like (+/-)-propranolol, tryptamine and spiperone recognize a single affinity component. These results suggest that the 5-HT1A binding site may exhibit at least two different affinity states depending upon its microenvironment and the intrinsic activity of the ligand used.
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PMID:Further evidence for differential affinity states of the serotonin1A receptor in rat hippocampus. 135 3

Constriction of carotid arteriovenous anastomoses is a common property of several antimigraine drugs. The present study concerns the effects of tertatolol (0.1, 0.3, 1 and 3 mg/kg i.v.), a novel beta-adrenoceptor antagonist with an agonist action on 5-HT1A receptors, on systemic haemodynamics and carotid blood flow distribution in the anaesthetized pig. Two other beta-adrenoceptor antagonists, one (propranolol) with and one (pindolol) without antimigraine actions, were compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal experimental model of migraine. While the beta-adrenoceptor antagonist with partial agonist action, pindolol, increased heart rate and cardiac output, propranolol and tertatolol decreased these variables moderately. Mean arterial blood pressure also decreased with the two highest doses of propranolol and with the highest dose of tertatolol. The calculated total peripheral conductance decreased with the first three doses of tertatolol. Carotid haemodynamic variables were not affected by pindolol, except for some increase in the nutrient fraction after the highest dose. Propranolol and especially tertatolol decreased both total carotid blood flow and arteriovenous anastomotic blood flow without affecting the nutrient fraction. In the case of tertatolol, blood flow decreases were accompanied by similar decreases in vascular conductance, indicating active arteriovenous anastomotic constriction. It is therefore suggested that tertatolol may prove effective in the treatment of migraine.
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PMID:Effects of tertatolol, a beta-adrenoceptor antagonist with agonist affinity at 5-HT1A receptors, in an animal model of migraine: comparison with propranolol and pindolol. 135 48

5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) facilitate motoneuron excitability through 5-HT1C/5-HT2 receptors in rats. Using spinal cord slices prepared from adult rats, we recorded unitary cell discharges, evoked by local stimulation of the adjacent site, extracellularly in the motor nuclei of the ventral horn. 5-MeODMT, DOI, 5-hydroxytryptamine (5-HT), 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) and tandospirone facilitated the probability of firing in the motor nuclei, with 5-MeODMT and DOI being the most potent. The effect of 5-MeODMT was significantly suppressed by ketanserin (a 5-HT2 receptor-selective antagonist), spiperone (a 5-HT1A/5-HT2 receptor antagonist) and cyproheptadine (a 5-HT1C/5-HT2 receptor antagonist), but not by 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, a 5-HT3 receptor-selective antagonist) or pindolol (a 5-HT1A/5-HT1B receptor antagonist). This suggests that 5-HT2 and/or 5-HT1C receptors are involved in the facilitatory effects of 5-HT receptor agonists on the synaptic activity of ventral horn cells.
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PMID:5-HT2/5-HT1C receptor-mediated facilitatory action on unit activity of ventral horn cells in rat spinal cord slices. 135 51

Amperozide is an atypical antipsychotic drug with high affinity for the serotonin 5-HT2 receptor but with low affinity for the dopamine D1 and D2 receptors. Amperozide dose-dependently increased the level of plasma corticocorticosterone in the rat. The effect of amperozide on plasma corticosterone was not inhibited by pretreatment with the 5-HT1A receptor antagonist pindolol or the 5-HT2 receptor antagonist ritanserin. Nor was it inhibited by the dopamine D2 receptor antagonist haloperidol. In contrast to ritanserin, amperozide did not antagonize plasma corticosterone elevation elicited by the serotonin receptor agonist MK-212. Similar to the serotonin uptake inhibitor fluoxetine, amperozide (0.5 mg/kg) significantly (p < 0.05) blocked p-chloroamphetamine (PCA) induced corticosterone release 4 and 16 hrs after amperozide administration. However, amperozide significantly increased the plasma corticosterone concentration also in rats pretreated with parachlorophenylalanine (PCPA). These data suggest that other mechanisms than a 5-HT uptake inhibitory effect are involved in the acute stimulation of corticosterone by amperozide.
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PMID:The effect of amperozide, a new antipsychotic drug, on plasma corticosterone concentration in the rat. 135 66

Evidence suggests that activation of 5-HT1A receptors leads to inhibition of 5-HT2-mediated behavior. The purpose of this study was to investigate the interaction between 5-HT1A and 5-HT2 receptor-mediated hormone secretion. Rats were pretreated with the 5-HT1A agonists buspirone (0, 0.5, 2.0 mg/kg, i.p.), 8-OH-DPAT (0, 0.05, 0.2 mg/kg, s.c.) or ipsapirone (0, 1.0, 2.5 mg/kg, i.p.), 45 min before decapitation. The 5-HT2 agonist DOI was administered (0-10 mg/kg, i.p.) 15 min after injection of the 5-HT1A agonists. The three 5-HT1A agonists differentially altered the DOI-induced increase of concentrations of hormone in plasma. None of the three 5-HT1A agonists influenced the basal levels of renin, ACTH and prolactin but 8-OH-DPAT and buspirone increased the basal level of corticosterone in plasma. Also, 8-OH-DPAT increased the effects of DOI on the concentration of ACTH in plasma but ipsapirone and buspirone did not. None of the 5-HT1A agonists significantly affected DOI-induced increase of concentration of corticosterone in plasma. Buspirone and 8-OH-DPAT potentiated the effect of DOI on prolactin in plasma, but ipsapirone did not. Ipsapirone potentiated the effect of DOI on the concentration of renin in plasma but this effect was not observed in 8-OH-DPAT- and buspirone-pretreated rats. The results do not support the hypothesis for a functional interaction between 5-HT1A and 5-HT2 receptors, since the three 5-HT1A agonists did not have the same influence on the hormonal effects of DOI.
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PMID:Neuroendocrine responses to the serotonin2 agonist DOI are differentially modified by three 5-HT1A agonists. 135 39

A fourteen-days treatment (twice a day) of male Wistar rats with the putative anxiolytic ipsapirone (10 mg/kg po) and the selective 5-HT1A agonist 8-OH-DPAT (1 mg/kg ip) induced changes in the turnover of serotonin and catecholamines in various regions of the brain. In contrast to 8-OH-DPAT, ipsapirone stimulated the development of tolerance in serotonin neurons in the hypothalamus, hippocampus, cortex and striatum. Nevertheless, adaptative changes were not produced by ipsapirone in dopamine neurons in the striatum or nucleus accumbens, or in noradrenaline neurons in the hypothalamus, hippocampus or cortex. The centrally active metabolite of ipsapirone 1-PP, which has adrenolytic properties, seems to be responsible for the effects on the dopamine and noradrenaline turnover.
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PMID:Effect of acute and chronic treatment of rats with the putative anxiolytic drug ipsapirone on the turnover of monoamine transmitters in various brain regions. A comparison with the 5-HT1A agonist 8-OH-DPAT. 135 15

Quantitative structure-activity relationships (QSAR) were analyzed for 5-HT1 and 5-HT1A affinity data of two series of 1-arylpiperazines. A conformational analysis of the investigated derivatives was performed using CNDO/2 method. It was shown that some 1-arylpiperazines adopt the bioactive conformations, while the others, like 1-(2-alkylphenyl)-piperazines, should exist in the twisted conformations at the receptor sites.
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PMID:Structure-activity relationship studies of CNS agents. Part III. On the bioactive conformations of 1-arylpiperazines at 5-HT1A receptor. 135 16

The general purpose of the present study was to analyze the possible interactions between the GABA-benzodiazepine and the serotonergic (5-HT) systems in the anxiolytic action of diazepam and the 5-HT1A agonists, ipsapirone, indorenate, and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effect of the benzodiazepine receptor antagonist, flumazenil (10.0 mg/kg), on the anxiolytic action of ipsapirone (5.0 mg/kg), indorenate (5.0 mg/kg), and 8-OH-DPAT (0.125 mg/kg) was examined on the avoidance exploratory behavior paradigm in mice. The effect of the 5-HT1 blockers, methiotepin (0.31 mg/kg), pindolol (3.1 mg/kg), and alprenolol (5.0 mg/kg), on the anxiolytic action of diazepam (0.5 mg/kg) was also studied. In the last part of this work, the putative potentiation between diazepam (0.25 mg/kg) and each of the serotonergic anxiolytics was investigated. The antianxiety effect of diazepam, ipsapirone, indorenate, and 8-OH-DPAT was prevented by flumazenil. The serotonergic/beta-blocker, alprenolol, partially antagonized the diazepam effect. Finally, a potentiation of suboptimal doses of diazepam and ipsapirone, but not with indorenate or 8-OH-DPAT, was observed. The findings suggest an interaction between both systems on the anxiolytic action of diazepam and the 5-HT1A agonists.
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PMID:Interaction of GABA and serotonin in the anxiolytic action of diazepam and serotonergic anxiolytics. 135 76

It has been established in experiments on spinal ganglia neurons of rats that 1-pyrimidinyl-piperazine derivatives show the properties of partial agonists of 5-HT1A-receptors. Some of them were discovered to be capable of blocking D2-dopamine receptors. Comparison of neuronal and behavioral activity of the substances tested has demonstrated that their anxiolytic activity detectable under the conditions of the conflict situation method significantly correlates with 5-HT1A-mimetic and anti-dopamine activity. The latter one correlates well with the influence of the substances tested on the time of immobilization in the forced swimming test.
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PMID:[The serotonin- and dopaminergic mechanisms in the action of 1-pyrimidinyl piperazine derivatives]. 136 Aug 56

We have used receptor autoradiography to investigate the distribution and pharmacological profile of non 5-HT1A/5-HT1C[3H]5-hydroxytryptamine binding sites in the brain of rabbits, hamsters and opossums. These data were compared to those found under similar conditions in the brain of rats and guinea pigs, species which are known to possess 5-HT1B and 5-HT1D receptors, respectively. In the presence of 100 nM 8-OH-DPAT and mesulergine, the regional distribution of [3H]5-hydroxytryptamine binding sites was very similar in the brain of all species investigated; densest labelling was observed in the globus pallidus, substantia nigra and superior colliculus. In all species, 5-carboxamidotryptamine competed for the labelled sites in a biphasic manner and metergoline displayed a subnanomolar affinity. In contrast, the beta-adrenoceptor blocking agents (-)propranolol, (-)pindolol, and (+/-)SDZ 21009 were potent displacers only in the rat, hamster and opossum brains. These data indicate that non 5-HT1A/5-HT1C[3H]5-HT binding sites display a high affinity for these agents in a particular rodent suborder as well as in opossum, a phylogenetically unrelated species.
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PMID:Non 5-HT1A/5-HT1C [3H]5-HT binding sites in the hamster, opossum, and rabbit brain show similar regional distribution but different sensitivity to beta-adrenoceptor antagonists. 136 Dec 46


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