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

1. Monoamine oxidase activity in platelets prepared from the blood of patients with iron-deficiency anaemia was significantly lowered when compared with that in platelets from normal subjects. 2. The Km values of the platelet enzyme for the substrates dopamine, 5-hydroxytryptamine, phenylethylamine and kynuramine were similar for the platelet enzyme from iron-deficient and normal groups. 3. Heat-in-activation studies showed that the platelet monoamine oxidase from iron-deficient subjects was more labile to this treatment, when compared with the platelet enzyme from normal subjects. 4. The sensitivity of platelet monoamine oxidase to the inhibitors, clorgyline and deprenil, was increased in iron-deficiency anaemia. 5. Binding studies with the 14C-binding irreversible monoamine oxidase inhibitor, deprenil, showed that the amount of enzyme capable of binding this inhibitor was lowered by 48% in platelets from iron-deficient patients when compared with platelets from normal subjects. 6. The results show that there is a lowered amount of active enzyme in platelets from iron-deficient subjects. It is suggested that iron is necessary either for the synthesis of monoamine oxidase apoenzyme or is a cofactor for an enzyme which attaches flavin-adenine dinucleotide covalently to the monoamine oxidase apoenzyme.
Clin Sci Mol Med 1976 Jun
PMID:Some properties of human platelet monoamine oxidase in iron-deficiency anaemia. 0 85

1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.
Clin Sci Mol Med 1978 Sep
PMID:Effects of the beta-receptor antagonists propranolol, oxprenolol and labetalol on human vascular smooth-muscle contraction. 2 41

1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.
Cell Mol Neurobiol 1992 Dec
PMID:Monoamine neurotransmitters and their metabolites in brain regions in Alzheimer's disease: a postmortem study. 128 63

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

In the mammalian nervous system, serotonin (5-hydroxytryptamine) binds to distinct cell surface receptor subtypes that are defined by their ligand binding and effector-coupling properties. The 5HT1c receptor is a G-protein coupled receptor that stimulates phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, leading to the mobilization of intracellular calcium and to the activation of protein kinase C. By using somatic cell hybrid analysis and FISH, we have mapped the HTR1C locus to the human X chromosome, band q24 and to the mouse X chromosome region D-F4. Comparison of these map positions offers new insights into the evolution of human and murine X chromosomes. Since HTR1C is expressed in certain parts of the central nervous system and abnormal function of the serotoninergic system has been implicated in affective disorders, obsessive-compulsive disorder and epilepsy, establishing the precise map position of HTR1C is an important first step toward evaluating this locus as a candidate for mutations in these syndromes and in X-linked mental disorders.
Hum Mol Genet 1992 Dec
PMID:Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). 130 5

In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline. The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of 5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin), 5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine. Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.
Mol Pharmacol 1992 Feb
PMID:Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors. 131 10

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 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

Aggregation of the IgE receptor on rat basophilic leukemia (RBL-2H3) cells triggers increased hydrolysis of polyphosphoinositides (PI), secretion of arachidonic acid (AA) and its metabolites, and degranulation to release 5-hydroxytryptamine. Despite the documented involvement of second messengers produced by the PI pathway in RBL cell exocytosis, recent evidence has suggested that additional signalling events are also necessary. We have, therefore, examined PLA2 activation and AA metabolite production by these cells in response to Ag stimulation, and evaluated the potential role of these in activating degranulation. The time course and antigen dose dependence for release of AA and its metabolites were comparable to those for degranulation and production of inositol phosphates (InsPs) when examined in parallel. Stimulated fatty acid release was highly selective for AA (compared with oleic or linoleic acids) and appeared to result predominantly from PLA2 activation. AA released upon antigen stimulation is rapidly metabolized to produce prostaglandin and leukotrienes. These are not required for activating degranulation, since BW755c completely inhibited AA metabolite production without affecting AA release, degranulation or InsP production. In contrast, the PLA2 inhibitors quinacrine and quercetin inhibited both AA release and degranulation in parallel, without significantly affecting levels of InsP production, and this inhibition could be partially reversed by exogenous addition of AA and lysophospholipid. These results demonstrate that activation of IgE-receptor mediated exocytosis of RBL cells does not require AA metabolites, and strongly suggest that PLA2 activation and release of AA and lysophospholipid may be involved in triggering this response.
Mol Immunol 1992 Nov
PMID:IgE receptor-mediated arachidonic acid release by rat basophilic leukemia (RBL-2H3) cells: possible role in activating degranulation. 132 76

Using the polymerase chain reaction amplification technique in conjunction with conventional cloning techniques, we have isolated a novel member of the serotonin [5-hydroxytryptamine (5-HT)] 1C/2 receptor subfamily (designated 5-HT2F) from rat stomach fundus. Two DNA fragments were amplified from cDNA synthesized from rat stomach fundus poly(A)+ RNA using the polymerase chain reaction technique with degenerate oligonucleotide primers derived from sequence comparisons of the second, third, and sixth putative transmembrane domains of known 5-HT receptors. These fragments were used as hybridization probes to isolate full length cDNA clones from rat stomach fundus cDNA libraries. Full length cDNA clones contained one open reading frame encoding a 479-amino acid protein with seven hydrophobic domains, characteristic of members of the guanine nucleotide-binding protein-coupled receptor superfamily. Within these seven putative transmembrane domains, the 5-HT2F receptor shared greatest homology with the rat 5-HT1C and 5-HT2 receptor subtypes (70% and 68%, respectively). Cell lines stably expressing the 5-HT2F receptor were established and demonstrated functional coupling to phosphatidylinositol hydrolysis upon 5-HT stimulation analagous to that observed for the 5-HT1C and 5-HT2 receptors. Membranes from the stably transfected cell lines (but not the untransfected parental lines) exhibited high affinity (Kd = 7.9 nM), saturable binding of [3H]5-HT. Maximum binding ranged from 0.1 to 2.4 pmol/mg of protein, depending on the clonal isolate. Using [3H]5-HT as the basis for a radioligand binding assay, the relative affinities of several tryptamine and piperazine derivatives for the cloned 5-HT2F receptor correlated with their relative potencies to contract the rat stomach fundus. These data suggest a probable relationship between this novel 5-HT2F receptor and the serotonin contractile receptor of the rat stomach fundus.
Mol Pharmacol 1992 Oct
PMID:Molecular cloning, functional expression, and pharmacological characterization of a novel serotonin receptor (5-hydroxytryptamine2F) from rat stomach fundus. 133 48


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