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)

Systemic administration of the neurotoxin 3-acetylpyridine (3-AP) to rats produced spontaneous episodes of spasmodic movement involving the trunk and limbs including torticollis, contortions of the trunk and rigid extension of the limbs. Because the neurotransmitter serotonin (5-HT) has been implicated in various human involuntary movement disorders, the functional and anatomical integrity of the 5-HT system in rats treated with 3-AP were examined. 5-HT-containing neurons in the brain stem were studied using immunohistochemical labeling with antiserum to 5-HT. Cells in the nucleus raphe obscurus were found to be altered following 3-AP treatment as shown by a decrease in 5-HT immunoreactivity as compared to control rats. No changes in 5-HT immunoreactivity were observed in any other region containing 5-HT cell bodies. Behaviorally, rats treated with 3-AP were 2.5-fold more sensitive to the ability of the 5-HT1A agonist 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.33-3.3 mg/kg) to produce the 5-HT syndrome. Similarly, 3-AP-treated rats were 2-fold more sensitive to the selective 5-HT2 agonist 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 0-1.0 mg/kg) at producing the head shake response. Although these behaviors associated with brain stem 5-HT receptors were potentiated by 3-AP, the hypothermic effect of 8-OH-DPAT which involves ascending mesencephalic 5-HT neurons was unchanged following 3-AP treatment. Treatment with 3-AP did not produce significant alterations of 5-HT or 5-hydroxyindoleacetic acid (5-HIAA) content in any brain region studied. Quantitative autoradiographic analysis of the density of 5-HT1A receptors labeled with [3H]8-OH-DPAT revealed that these sites were unchanged in regions of the brain (frontal cortex, hippocampus and brain stem) and in the spinal cord. Similarly, few changes in the density of 5-HT2 receptors measured with [3H]ketanserin were observed in various brain regions. These results suggest that neurons from the nucleus raphe obscurus are involved in the elicitation of 5-HT-mediated behavioral responses by 5-HT1A and 5-HT2 receptor agonists that are though to be mediated through brain stem and spinal cord mechanisms. In addition, because of the close neuroanatomical relationship of the nucleus raphe obscurus with various brain regions known to be involved in motor control, the destruction of this region by 3-AP may contribute to the spasmodic motor behaviors observed following 3-AP treatment.
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PMID:Destruction of the nucleus raphe obscurus and potentiation of serotonin-mediated behaviors following administration of the neurotoxin 3-acetylpyridine. 169 5

Rats treated chronically (14 days) with the 5-HT2 receptor antagonist ritanserin, show decreased 5-HT2 receptor numbers in the frontal cortex. The present experiments were designed to investigate the effects of acute and chronic ritanserin treatment on the autoregulatory control of the release of 5-HT and its metabolite 5-HIAA in vivo in rats using intracerebral dialysis. Neither acute nor chronic ritanserin treatment altered basal extracellular levels of 5-HT or 5-HIAA, suggesting that 5-HT2 receptors do not directly influence 5-HT release. In the control animals, systemic stimulation of somatodendritic 5-HT1A receptors with the 5-HT1A receptor agonist 8-OH-DPAT, inhibited the release of 5-HT presumably via inhibitory feedback autoregulation; an effect also seen in animals treated acutely with ritanserin. However, in the animals treated chronically with ritanserin, administration of 8-OH-DPAT produced an initial increase in extracellular 5-HT which declined gradually to the end of the experiment. These results suggest that chronic, but not acute, 5-HT2 receptor antagonist treatment attenuates the 5-HT1A receptor-mediated autoregulation of 5-HT release. The underlying mechanisms have yet to be ascertained.
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PMID:Chronic 5-HT2 receptor antagonist treatment alters 5-HT1A autoregulatory control of 5-HT release in rat brain in vivo. 170 42

Previous works have indicated that insulin stress activates the serotonin (5-HT) and sympathoadrenal systems in the fasted rat. In addition, recent studies have shown that activation of either the 5-HT1A, the 5-HT1C or the 5-HT2 receptor triggers adrenal catecholamine release. Then, the aim of this study was to investigate whether brain 5-HT, by means of these receptors, mediates insulin-induced adrenal catecholamine release. For that purpose, both plasma epinephrine (Epi), norepinephrine (NE) and glucose levels were measured in conscious rats bearing intracardiac catheters. The intravenous administration of insulin (1 IU/kg) triggered hypoglycemia throughout the following 120 min in both fed and overnight fasted rats. Insulin stress elicited within 30 min a 5- and 38-fold increase in plasma Epi levels in fed and fasted rats, respectively. This change was associated with significant elevations in plasma NE levels in the fasted rats only. The intravenous administration of the mixed 5-HT1A receptor/beta-adrenoceptor blocker (-)-propranolol (5 mg/kg) to fasted rats did not modify plasma glucose and catecholamine peak responses to insulin; however, at later times, insulin triggered hypoglycemic convulsions in (-)-propranolol- but not in saline-pretreated rats. Besides, pretreatments with the 5-HT1C/5-HT2 receptor blocker LY 53857 (0.5 mg/kg), or the 5-HT1/5-HT2 receptor antagonist metergoline (3 mg/kg), did not diminish plasma catecholamine responses to insulin stress. Similarly, none of these antagonists affected plasma glucose recovery. These results seem to indicate that the sympathoadrenal response to insulin administration is not mediated by 5-HT.
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PMID:Influence of 5-HT1 and 5-HT2 receptor antagonists on insulin-induced adrenomedullary catecholamine release. 178 47

1. The effects of microinjections (100 nl) into the dorsal motor vagal nucleus of the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan, the 5-HT2 receptor agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), the 5-HT3 receptor agonist phenylbiguanide (PBG), the alpha 2-adrenoceptor agonist clonidine and the excitatory amino acid glutamate on heart rate, blood pressure, tracheal pressure and phrenic nerve activity were investigated in atenolol-pretreated rats anaesthetized with sodium pentobarbitone. 2. Microinjections of glutamate (2.5 nmol) caused decreases in blood pressure, heart rate and phrenic nerve activity. In contrast, microinjections of 5-HT (1.2 nmol), 8-OH-DPAT (1.2 nmol) and flesinoxan (1.3 nmol) all caused a bradycardia but had no effect on blood pressure. In addition, 8-OH-DPAT and flesinoxan caused an increase in phrenic nerve activity. 3. Microinjections of DOI, PBG and clonidine had no significant effect on any of the variables recorded. None of the drugs used had any significant effect on tracheal pressure. 4. These results support the hypothesis that activation of 5-HT1A receptors causes excitation of cardiac vagal motoneurones and suggest that these receptors are also important in the control of central respiratory drive.
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PMID:Microinjections of 5-HT1A agonists into the dorsal motor vagal nucleus produce a bradycardia in the atenolol-pretreated anaesthetized rat. 179 13

While it had no effect on the resting tension of mouse tracheal segments, 5-HT (10(-8)-10(-4) M) potentiated concentration dependently the contractions induced by electrical field stimulation (EFS). The maximal potentiation was 105 +/- 38% and the EC50 value was 1.4 +/- 0.6 x 10(-6) M (n = 6). The responsiveness of mouse trachea to acetylcholine was not altered by 5-HT (10(-5) M). The 5-HT1A,B antagonist pindolol (10(-6) M), the combined 5-HT2 and 5-HT1C receptor antagonist, ketanserin (10(-6) M), or the combined 5-HT1 and 5-HT2 receptor antagonist, methysergide (10(-6) M), all partially inhibited the effect of 5-HT on the twitch responses. Blockade of 5-HT3 receptors by GR 38032F (10(-6) M) did not affect the potentiation by 5-HT. Antagonism of 5-HT3 and 5-HT4 receptors by ICS 205,930 (3 x 10(-6) M) increased the potentiation of the twitch responses by 5-HT, this was probably due to a decrease of the baseline EFS-induced twitch response by ICS 205,930. Alkylation of the 5-HT2 receptor by phenoxybenzamine (3 x 10(-7) M) treatment did not significantly affect the potentiation of the twitch responses by 5-HT. The beta-adrenoceptor antagonist, timolol (10(-6) M), and the alpha-adrenoceptor antagonist, phentolamine (10(-6) M), did not influence the potentiation of the twitch responses by 5-HT, excluding the involvement of the adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-HT1-like receptors mediate potentiation of cholinergic nerve-mediated contraction of isolated mouse trachea. 179 65

The 5-hydroxytryptamine (5-HT) receptor by which 5-HT can evoke nonadrenergic noncholinergic (NANC) relaxations in isolated guinea-pig proximal colon was characterized using a variety of 5-HT receptor agonists and antagonists. In the presence of atropine (0.2 microM), guanethidine (5 microM) and ketanserin (10 microM), a concentration-dependent relaxation was obtained with 5-HT (apparent mean pEC50 value 6.43), 5-CT (5.64) and 5-CH3-T (5.02); 8-OH-DPAT, TFMPP, GR43175 and 5-OCH3-N,N-DMT (up to 100 microM) did not relax the guinea-pig proximal colon. The nonselective 5-HT receptor antagonist, metitepine (0.1 microM), the 5-HT1C/5-HT2 receptor antagonists, mianserin (1 microM) and pizotifen (0.1 microM), and the 5-HT1A/5-HT2 receptor antagonists spiperone (3 microM) shifted the concentration-response curves for 5-HT to the right. The 5-HT1A/5-HT1B receptor antagonist, cyanopindolol (0.3 microM) and a selective 5-HT3 receptor antagonist, ICS205-930 (1 microM) failed to block the 5-HT-induced NANC relaxation. In conclusion, the experiments with agonists and antagonists are compatible with the view that a 5-HT1-like receptor is involved in 5-HT-induced NANC relaxations of the guinea-pig proximal colon.
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PMID:Characterization of 5-hydroxytryptamine-induced relaxations of guinea-pig proximal colon. 181 62

Both intravenous and central administration of ketanserin, a 5-HT2 receptor antagonist, decrease blood pressure and sympathetic nerve activity, suggesting a central origin of its effects. However, ketanserin also possesses alpha 1-adrenoceptor blocking properties. Selective 5-HT2 receptor antagonists devoid of alpha 1-adrenoceptor blocking properties, e.g. LY 53857 and cinanserin, fail to reduce blood pressure and sympathetic nerve activity. In addition, 5-HT2 receptor agonists increase blood pressure and sympathetic nerve discharge. Therefore, it seems improbable that blockade of central 5-HT2 receptors alone could lead to a reduction in blood pressure. In contrast, the selective 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan decrease blood pressure and heart rate by a centrally-mediated decrease in sympathetic tone and an increase in vagal tone. The sympatho-inhibitory effects of 5-HT1A receptor agonists result from the stimulation of postsynaptic 5-HT1A receptors within the ventrolateral pressor area. These results suggest that selective 5-HT1A receptor agonists acting in the central nervous system could be developed for the treatment of hypertension. Indeed, drugs such as flesinoxan and urapidil are effective in this setting.
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PMID:Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation. 181 50

The three dimensional structure, electrostatic potentials and molecular dynamics of a series of tricyclic antipsychotic drugs and metabolites were examined by computer graphics and molecular modeling techniques. Three dimensional models of the 5-HT1A and 5-HT2 receptor and of the dopamine D2 receptor were constructed from the amino acid sequences. The receptor models have strongly negative electrostatic potentials around the synaptic domains and a postulated ligand binding site. This indicates that protonated ligands are attracted to these receptors by electrostatic forces. Pharmacologically inactive trans(E)-thioxanthenes and phenothiazine ring sulphoxides had strongly negative electrostatic potentials around a part of the ring system. This may weaken their electrostatic interactions with the D2 receptor, and be the reason for their lack of potency in D2 receptor binding and related pharmacological tests. Molecular dynamics simulations in aqueous solution demonstrated that both the side chains and the tricyclic ring systems of the drugs are highly flexible, and move between different conformations in picoseconds.
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PMID:Molecular modeling of antipsychotic drugs and G protein coupled receptors. 181 51

The effect of the serotonergic receptor agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP) was studied on the K(+)-evoked [3H]acetylcholine [( 3H]ACh) release from guinea pig hippocampal synaptosomes loaded with [3H]choline. TFMPP (5-1,000 microM) inhibited the evoked ACh release in a dose-dependent manner (IC50 = 81.8 microM). The inhibitory effect of TFMPP was mimicked by CGS-12066B (10, 30, and 100 microM), a 5-hydroxytryptamine1B (5-HT1B)/5-HT1D receptor agonist; 1-(m-chlorophenyl)piperazine (100 microM), a 5-HT1C/5-HT1B receptor agonist; and 5-carboxamidotryptamine (10 microM), a nonselective 5-HT1 receptor agonist. 8-Hydroxy-2-(di-n-propylamino)tetralin (10 and 100 microM), a 5-HT1A receptor agonist, and quipazine (10 and 100 microM), a 5-HT2 receptor agonist, did not have any significant effect. Serotonergic antagonists, such as dihydroergotamine (0.1 and 1 microM), metergoline (0.1 microM), methysergide (0.5 and 1 microM), or yohimbine (1 and 10 microM), blocked the TFMPP effect dose-dependently. In contrast, methiotepine (0.3 and 1 microM), propranolol (1 microM), ketanserin (0.1 microM), mesulergine (0.1 microM), ICS 205930 (0.1 and 1 microM), and spiroperidol (1 and 7 microM) did not affect the TFMPP-induced inhibition of the evoked ACh release. These data suggest that, in guinea pig hippocampus, the K(+)-evoked ACh release is modulated by a 5-HT1 receptor distinct from the 5-HT1A, 5-HT1B, and 5-HT1C subtypes.
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PMID:The inhibitory effect of trifluoromethylphenylpiperazine on [3H]acetylcholine release in guinea pig hippocampal synaptosomes is mediated by a 5-hydroxytryptamine1 receptor distinct from 1A, 1B, and 1C subtypes. 182 81

The effects of 5-hydroxytryptamine (5-HT) and of a number of 5-HT receptor agonists and antagonists on the release of endogenous aspartate were investigated in rat cerebellum slices and synaptosomes depolarized with high K+. The release of endogenous aspartate evoked from slices by 35 mmol/l KCl and from synaptosomes by 15 mmol/l KCl was strongly (about 90%) calcium-dependent. In slices the release of aspartate was inhibited by exogenous 5-HT (0.1-100 nmol/l) in a concentration-dependent manner. The indoleamine was very potent, producing 30% inhibition at 0.1 nmol/l. The effect of 10 nmol/l 5-HT was partly but maximally counteracted by ketanserin (300-1000 nmol/l), a 5-HT2 receptor antagonist, but fully blocked by 300 nmol/l of the mixed 5-HT1/5-HT2 receptor antagonist methiothepin. The 5-HT1A receptor agonist 5-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibited the K(+)-evoked release of endogenous aspartate in a concentration-dependent manner. The effect of 8-OH-DPAT was antagonized by methiothepin, but not by ketanserin which fully antagonized the inhibition produced by DOI. In cerebellar synaptosomes the release of endogenous aspartate evoked by 15 mmol/l K+ was inhibited by exogenous 5-HT and by 8-OH-DPAT, but not by DOI. Methiothepin (100-300 nmol/l) antagonized the inhibitory effects of 100 nmol/l 5-HT or 8-OH-DPAT. However, 1000 nmol/l of various 5-HT receptor antagonists [ketanserin, methysergide, (--)-propranolol, spiperone or ICS 205-930] did not counteract the effect of 100 nmol/l 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of endogenous aspartate from rat cerebellum slices and synaptosomes: inhibition mediated by a 5-HT2 receptor and by a 5-HT1 receptor of a possibly novel subtype. 183 Sep 29


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