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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to study the control of vasopressin-release, the effect of a series of potential agents was studied in an in vitro perifusion system of rat neurohypophysis after in vivo treatment with nialamide, a monoamine oxidase inhibitor. In this system, metlatonin stimulated vasopressin-release in a dose-dependent manner (1 x 10-8 to 1 x 10-3 M). Serotonin (1 x 10-3 M) also led to a significant increase of vasopressin-release whereas quipazine (1 x 10-3 M), a putative serotonin agonist and monoamine oxidase inhibitor, caused a 3-fold stimulation of the release of the neurohormone. The stimulatory effects of melatonin and serotonin were prevented by omission of Ca2+ combined to an excess of Mg2+ (12mM) in the perifusion medium. 1 x 10-6 M somatostatin did not affect basal or melatonin-stimulated vasopressin-release. These results show that melatonin and serotonin can have a direct stimulatory effect on vasopressin release at the neurohypophyseal level.
Mol Cell Endocrinol 1979 May
PMID:Melatonin-and serotonin-stimulated release of vasopressin from rat neurohypophysis in vitro. 46 80

The interaction of arginine vasotocin (AVT) and norepinephrine (NE) upon pineal gland indoleamine synthesis was investigated. Rat pineal glands were incubated for 10 h in Krebs--Ringer bicarbonate plus 2 mg/ml glucose, 1 mg/ml bovine serum albumin, [14C]tryptophan, NE (10(-6) M), and log doses of AVT ranging from 100 ng to 10 microgram. Incubation media were extracted for [14C]serotonin while the other [14C]indoleamines, melatonin, hydroxyindoleacetic acid (HIAA), methoxyindoleacetic acid (MIAA), N-acetylserotonin (NAS), hydroxytryptophol (HTOL), and methoxytryptophol (MTOH) were separated by thin-layer chromatography. Serotonin metabolism was decreased by 0.1 microgram AVT and NAS decreased by 1.0 microgram AVT. Melatonin synthesis was decreased by both 0.1 and 1.0 microgram AVT. AVT also decreased the conversion of [14C]serotonin to MIAA and to HTOL. The data indicates that AVT decreased NE-stimulated pineal indoleamine synthesis in vitro and further suggests that AVT may participate in the intracellular regulation of melatonin synthesis.
Mol Cell Endocrinol 1978 Jun
PMID:Interaction of arginine vasotocin and norepinephrine upon pineal indoleamine synthesis in vitro. 68 Mar 35

1. Studies with a sensitive radioenzymatic assay for plasma noradrenaline suggest there is a selective overactivity of the sympathetic nerous system in essential hypertension. 2. Serotonin turnover in the mesenteric vessels is approximately twice that of noradrenaline and it is suggested that serotonin may interact with noradrenaline to maintain vascular resistance. 3. Methodology which allows the study of local sympathetic turnover in nuclei of the central nerous system and in peripheral blood vessels is decribed. This approach has been used to study non-innervated sympathetic turnover observed in phaceochromocytoma.
Clin Sci Mol Med Suppl 1976 Dec
PMID:The role of noradrenaline and other transmitter hormones in the pathogenesis of hypertension. 79 56

The biogenic amines, serotonin (5-HT) and norepinephrine, activate follicular cells and are endogenous thyroid constitutents. Both amines are taken up by throid lobes incubated in vitro. Uptake of 5-HT is temperature and concentration dependent, is inhibited by chlorimipramine more than by desmethylimipramine, and although it is inhibited by norepinephrine, 5-HT uptake is unaffected by chemical sympathetomy with 6-hydroxydopamine. Electron microscopic radioautography reveals that follicular cells are responsible for uptake of 5-HT and adrenergic nerves for uptake of norepinephrine. These data are consistent with the hypothesis that biogenic amines are intrathyroidal transmitters acting on follicular cells, and that uptake mechanisms may contribute to their inactivation.
Mol Cell Endocrinol
PMID:Uptake of biogenic amines by thyroid glands. 95 49

Immunocytochemical localization of 5-hydroxytryptamine (5-HT) in the nervous system and aggregate tissue cultures was performed employing an antibody to 6-OH-1,2,3,4-tetrahydro-beta-carboline. A number of immunochemical and biochemical tests with the antigen and the antibody and some procedural changes in the methodology applied for immunolocalization revealed the anti-5-HT-like affinity of the antibody, if applied in paraformaldehyde-fixed tissues. Studies in the hypothalamus, striatum, brainstem, spinal cord, and pineal gland show the complexities of the serotoninergic system. Ultrastructural immunocytochemistry with the preembedding technique reveals that 5-HT synapses are of the asymmetric type. The presynaptic element contains clear, round, small vesicles, with some large dense-core vesicles. The contacts are made with the somata and primary, secondary dendrites or with spines of non-5-HT neurons. Presynaptic dendrites are found in the n. raphe dorsalis, contacting non-5-HT dendrites. Double immunocytochemical methods demonstrated contacts of 5-HT fibers on enkephalin containing neurons of the spinal trigeminal nucleus and on somatostatin containing neurons of the medullary reticular formation. In vitro studies of cultured mesencephalic neurons were performed with the method of aggregating cultures. Such development of a miniature organized nerve tissue was followed up to 35 d in culture. Organization of the neuropil and synaptogenesis was studied using standard electron microscopy. The differentiation of neurons and astrocytes was studied using antibodies to 5-HT and GFAP. Serotonin immunoreactivity could be observed in neuronal bodies and processes at light microscope level as early as the fourth day of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Neurobiol 1992
PMID:Antibodies as molecular probes in neurobiology. Identification of chemically defined neurons and synapses in tissues and tissue cultures. 128 32

The development of the new ligand serotonin-5-O-carboxymethyl-glycyl [125I]tyrosinamide (abbreviated [125I]GTI) allows for the direct visualization of serotonin1B and serotonin1D (5-HT1B/1D) sites. Autoradiographic techniques were used to demonstrate the selective binding of this ligand to 5-HT1D sites in human post-mortem brain materials. The distribution of [125I]GTI binding sites was compared to [3H]5-HT sites in the presence of different displacers. The results show the selective binding of [125I]GTI to sites in the basal ganglia and substantia nigra which corresponds to 5-HT1D receptors.
Brain Res Mol Brain Res 1992 Mar
PMID:Direct visualization of serotonin1D receptors in the human brain using a new iodinated radioligand. 131 14

Serotonin (5-hydroxytryptamine; 5-HT) mediates many central and peripheral nervous system functions by its interaction with specific neuronal receptors. Here we report the genomic structure of the human 5-HT2 receptor. The SacI-EcoRI restriction fragment of rat 5-HT2 receptor cDNA was used as a probe to identify and isolate two positive clones of 8.5 and 7.0 kb from an EcoRI restriction digest of a chromosome 13 specific EcoRI fragment lambda-phage human genomic library. Subcloning and sequencing of these fragments showed the 8.5 kb fragment (designated lambda SE-5) contained the first two exons of the 5-HT2 receptor gene. The 7.0 kb insert (lambda SE-2) contained an incomplete third exon. A HindIII-EcoRI fragment of this insert was used as a probe to isolate a 9.0 kb clone (lambda SH-2), which contained the entire third exon, from a chromosome 13 specific HindIII-fragment lambda-phage human genomic library. The isolation of these three clones (lambda SE-5, lambda SE-2 and lambda SH-2) shows that the human 5-HT2 receptor gene consists of three exons separated by two introns and spans over 20 kb. The deduced amino acid sequence of the human, mouse and rat 5-HT2 receptors are highly conserved and all three share a 90% sequence similarity.
Brain Res Mol Brain Res 1992 Jun
PMID:The human 5-HT2 receptor is encoded by a multiple intron-exon gene. 132 14

The canine RDC4 gene was used to isolate two distinct human serotonin receptor genes. The receptor encoded by clone RH-6 was the species homolog of RDC4 and was identical to a human serotonin 5-hydroxytryptamine1D (5-HT1D) receptor that was recently reported [Mol. Pharmacol. 40:143-148 (1991)]. The receptor encoded by RH-2 was a novel 5-HT receptor that was 61% identical to RH-6 and showed the greatest homology with the rat 5-HT1B receptor sequence (94%). The RH-2 gene contained an intronless, 1170-base pair, open reading frame that encoded a 390-amino acid protein that contained all of the hallmarks of a guanine nucleotide-binding protein-linked receptor. Heterologous expression of the RH-2 gene in Chinese hamster ovary cells led to the appearance of high affinity binding sites for 5-HT (Kd = 2.6 nM, Bmax = 2.9 pmol/mg of membrane protein), and the receptor expressed in Chinese hamster ovary cells was coupled to inhibition of adenylyl cyclase. Competition binding experiments using compounds that are selective for various 5-HT receptor subtypes showed the highest correlation with a 5-HT1D-like receptor (r = 0.89) and a low correlation with 5-HT1B-like receptors. Examples of the 5-HT1D-like pharmacology displayed by RH-2 include high affinity for the 5-HT1D-selective compound sumatriptan (Ki = 9.4 nM) and for the alpha 2-adrenergic receptor antagonist rauwolscine (Ki = 47 nM). Therefore, despite the close genetic relationship between RH-2 and the rat 5-HT1B receptor, our results indicate that the receptor encoded by RH-2 2 is best classified as a human 5-HT1D receptor subtype and defines a second member of the human 5-HT1D receptor family.
Mol Pharmacol 1992 Sep
PMID:Cloning and pharmacological characterization of a novel human 5-hydroxytryptamine1D receptor subtype. 132 44

The density of 5-hydroxytryptamine (5-HT)1B receptors and their coupling to the inhibition of cAMP accumulation were investigated in opossum kidney cells maintained in culture. The density and properties of the receptor were determined using [125I] iodocyanopindolol as the radioligand. The pharmacological specificity of the binding site was consistent with that expected for a 5-HT1B receptor. Serotonin inhibited forskolin-stimulated cAMP accumulation with an EC50 of 4-8 nM. Compounds known to show selectivity at the 5-HT1B receptor, such as trifluoromethyl-phenylpiperazine and CGS-12066B, also inhibited forskolin-stimulated cAMP accumulation, acting as full agonists with efficacies comparable to that of serotonin. Other beta-adrenergic receptor antagonists, including (-)-pindolol and (-)-alprenolol, bound to the receptor with high affinity and acted as partial agonists capable of inhibiting forskolin-stimulated cAMP accumulation. Exposure of cells to 5-HT resulted in a time- and dose-dependent decrease in the density of 5-HT1B receptors that was not accompanied by a change in the Kd of the binding site for [125I] iodocyanopindolol. A maximum decrease of 60% in the number of 5-HT1B receptors was evident after a 16-hr treatment with 1 microM 5-HT. Concomitant with the observed decrease in the density of receptors was a marked increase in the EC50 for 5-HT-mediated inhibition of forskolin-stimulated cAMP accumulation. The EC50 was increased 4-5-fold after a 16-hr exposure to 1 microM 5-HT, and the maximal level of inhibition was markedly decreased. Whereas pretreatment with moderate concentrations of 5-HT (100-300 nM) for 16 hr produced significant decreases in the density of 5-HT1B receptors and increases in the EC50 for inhibition of forskolin-stimulated cAMP formation, there was little change in the maximal level of inhibition that could be attained. Such a combination of changes could be explained by the presence of "spare" 5-HT1B receptors on these cells.
Mol Pharmacol 1992 Sep
PMID:Regulation of the 5-hydroxytryptamine1B receptor in opossum kidney cells after exposure to agonists. 132 46

A three-dimensional model of the serotonin (5-hydroxytrytamine; 5-HT) 5-HT2 receptor was constructed from the amino acid sequence by molecular graphics techniques, molecular mechanics energy calculations and molecular dynamics simulations. The receptor model has 7 alpha helical segments which form a membrane-spanning duct with a putative ligand binding site. Most of the synaptic domains and the ligand binding site were surrounded by negative electrostatic potentials, suggesting that positively charged ligands are attracted to the receptor by electrostatic forces. The cytoplasmic domains, except the C-terminal tail, had mainly positive electrostatic potentials. The molecular dynamics of the receptor-ligand complex was examined in 100 ps simulations with 5-HT or ritanserin at a postulated binding site. During the simulations the helices moved from an initial circular arrangement into a more oval arrangement, and became slightly tilted relative to each other. The protonated ligands neutralized the negative electrostatic potentials around Asp 120 and Asp 155 in the central core of the receptor. 5-HT had only weak interactions with Asp 155 but strong interactions with Asp 120 during the simulations, with the amino group of 5-HT tightly bound to the carboxylic side chain of Asp 120. Ritanserin showed similarly strong interactions with Asp 120 and Asp 155 during the simulations.
Brain Res Mol Brain Res 1992 Jul
PMID:Molecular dynamics of serotonin and ritanserin interacting with the 5-HT2 receptor. 133 49


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