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

Human serotonin [5-hydroxytryptamine (5-HT)1A] receptors have been transfected in NIH-3T3 cells, and their pharmacology and coupling to adenylyl cyclase have been analyzed. Three cellular preparations were used, 1) monoclonal cell lines (clones 6, 2B, and 4B), expressing 45, 280, and 500 fmol of 5-HT1A receptors/mg of protein, respectively; 2) clones 6, 2B, and 4B in which the concentration of 5-HT1A receptors was increased after stimulation of the glucocorticoid-inducible promoter with dexamethasone; and 3) polyclonal cell lines that expressed an increasing amount of 5-HT1A receptor as a function of cell passage. The transfected 5-HT1A receptors inhibited basal, forskolin-stimulated, and isoproterenol-stimulated adenylyl cyclase. The inhibition was dependent on the receptor density expressed, increasing from 60% at low density (45 fmol/mg) to 90% at a density higher than 280 fmol/mg. The pharmacology of the 5-HT1A receptor was studied, with particular attention being paid to the behavior of some agonists. These pharmacological characteristics are similar to those of 5-HT1A receptors in hippocampus but different from those of 5-HT1A in cerebral cortex. Analysis of the potencies and efficacies of the full agonist 5-HT and the partial agonist ipsapirone, as a function of receptor density in the three cellular populations used, revealed that 1) the efficacies of the full and partial agonists increased with the receptor density; 2) the EC50 values of the full and partial agonists were not shifted to the left when the receptor density was increased (based on the increase in efficacy and considering the classical pharmacological models of receptor-drug action, a 9-10-fold shift was expected); and 3) the ratio between the efficacies of the full agonist 5-HT and the partial agonist ipsapirone was not modified when the receptor concentration was increased or when the GTP-binding protein availability was decreased. The results indicate that neither the classical nor the operational model of drug-receptor action can be used to describe the coupling of 5-HT1A receptors to adenylyl cyclase in transfected NIH-3T3 cells. One of the explanations could be that 5-HT1A receptors and GTP-binding proteins are coupled in functional domains (almost precoupled), rather than distributed in homogeneous compartments in which they are free to diffuse.
Mol Pharmacol 1992 Jun
PMID:Transfection of human 5-hydroxytryptamine1A receptors in NIH-3T3 fibroblasts: effects of increasing receptor density on the coupling of 5-hydroxytryptamine1A receptors to adenylyl cyclase. 161 16

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) exerts diverse physiological effects in the central and peripheral nervous systems and in smooth muscle by interacting with pharmacologically distinct membrane receptors. We report here the cDNA cloning of the mouse 5-HT1C receptor and its functional expression in Xenopus oocytes. This receptor possesses the unusual feature of containing eight hydrophobic domains capable of forming membrane-spanning alpha-helices, contrary to the usual '7-helix' paradigm for other membrane receptors that function through coupling to GTP-binding proteins. By hybridization analysis of Chinese hamster x mouse somatic cell hybrid lines, the gene for the receptor, designated Htr1c, has been assigned to the mouse X chromosome.
Brain Res Mol Brain Res 1991 Sep
PMID:The mouse 5-HT1C receptor contains eight hydrophobic domains and is X-linked. 166 11

Porphyrin and indole metabolism was studied in the Harderian glands of Syrian hamsters during the proestrous and estrous stages of the estrous cycle. Porphyrins remained unaltered during these stages, but levels of different indoles (5-hydroxytryptophan, 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine, and 5-hydroxyindole acetic acid) exhibited pronounced changes during the dark:light period in both proestrous and estrous. There was a strong parallelism between 5-hydroxytryptamine, N-acetyl-5-hydroxytryptamine and 5-hydroxyindole acetic acid levels. Hydroxytryptophan rhythms appeared slightly shifted from those of the other indoles. Immunoreactive melatonin present in the Harderian glands did not show a significant day-night change during the stages studied.
J Steroid Biochem Mol Biol 1991 Jan
PMID:Indole and porphyrin content of the Syrian hamster harderian glands during the proestrous and estrous phases of the estrous cycle. 170 41

It was found in experiments on isolated dorsal root ganglion neurons of rats that dopamine (10(-8)-10(-6) Mol/l) potentiated depolarizing neuronal responses evoked by injection of 5-hydroxytryptamine from micropipette. Similar concentrations of 5-hydroxytryptamine (10(-8)-10(-6) Mol/l) potentiated neuronal depolarizing responses evoked by dopamine. Potentiating action of monoamines on combined neuronal responses depended on concentration and was inhibited by antagonists of dopamine (haloperidol) and 5-hydroxytryptamine (deseril) receptors. This effect of monoamines had postsynaptic nature and was bound with an increase of Ca2+ and cAMP intracellular concentrations.
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PMID:[Reciprocal modulating effect of serotonin and dopamine on neurons of rat spinal ganglia]. 187 9

The JCR:LA-cp rat is a strain carrying the mutant cp (corpulent) gene. Animals that are homozygous cp are hyperphagous, hyperinsulinemic, hyperlipidemic, and obese. Corpulent male rats, but not females or lean rats, develop atherosclerotic lesions and myocardial lesions. Since the myocardial lesions are apparently of ischemic origin, the noradrenergic system and vascular hyperactivity and vasospasm may play a role in the pathogenesis. To test this we have studied the brain contents of the amines norepinephrine, dopamine, and 5-hydroxtryptamine and their breakdown products and depleted the peripheral sympathetic terminals with 6-hydroxydopamine. Only 5-hydroxytryptamine and 5 hydroxyindole-3-acetic acid were present at higher concentrations in the corpulent rats with depressed levels of dopamine in very young or old lean rats. The activity of monoamine oxidase may provide an indication of nonadrenergic activity in tissue. The activity in the heart increased with age and was higher in the corpulent rats than in the lean at all ages. Activity in aorta was independent of age or genotype. Long term treatment with 6-hydroxydopamine caused marked depletion of norepinephrine in the heart with only a slight decrease in brain concentration. There were no effects on the hyperlipidemia or hyperinsulinemia that are strongly associated with vascular and myocardial disease. The myocardial lesion frequency in corpulent rats was not altered by the chemical sympathectomy. The results suggest that norepinephrine and the sympathetic nervous system are probably not involved in the generation of the myocardial lesions or metabolic abnormalities in this strain of rat.
Exp Mol Pathol 1991 Feb
PMID:Myocardial disease and catecholamine metabolism in JCR:LA-corpulent rat. 189 32

Serotonin (5-hydroxytryptamine) functions as a neurotransmitter and a hormone. Its diverse actions are mediated by at least seven distinct cell surface receptor subtypes. The serotonin receptor subtype 2 (gene symbol HTR2) is a G-protein-coupled receptor, expressed primarily in the cerebral cortex, where upon stimulation it stimulates the hydrolysis of inositol phospholipids. We have mapped the HTR2 locus to human chromosome 13 and to mouse chromosome 14 by somatic cell hybrid analysis. Linkage studies in CEPH families, using a PvuII RFLP detected with the HTR2 probe, revealed tight linkage between HTR2 and ESD, the locus for esterase D. The most likely position for HTR2 is between ESD and RB1, the retinoblastoma-1 gene. The homologous loci in mouse, Rb-1 and Esd(Es-10) are on mouse chromosome 14, close to ag, agitans, a recessive neurological mutation. Having mapped Htr-2 to mouse chromosome 14, we predict that it falls into this known conserved gene cluster.
Somat Cell Mol Genet 1990 Nov
PMID:The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14. 198 30

The capacity of different lung parenchymal cells to accumulate putrescine was investigated by incubating slices of rat lung in a medium containing the tritiated compound. Quantitative examination of autoradiographs, by electron microscopy, indicated that accumulation of putrescine occurred in both the Type I and Type II cells of the alveolar epithelium. Putrescine uptake was abolished by the addition of spermidine to the medium or by incubating at 0 degrees C. Lung samples from rats dosed with the pneumotoxin O,S,S-trimethyl phosphorodithioate (OSSMeO), which selectively damages Type I pneumocytes, showed a large reduction in the uptake of label by both Type I and Type II cells. This treatment also resulted in an increase in the labeling of alveolar macrophages. Control samples, from undosed rats, were incubated in medium containing tritiated 5-hydroxytryptamine; this compound did not accumulate in epithelial cells but it was concentrated in the endothelium of the alveolar capillaries and in the blood cells within these vessels. The demonstration of putrescine uptake by both Type I and Type II pneumocytes, together with its reduction by dosing with OSSMeO, has vindicated the use of this activity, in lung slices, as an index of damage to the alveolar epithelium.
Exp Mol Pathol 1991 Jun
PMID:Effects of injury on [3H]putrescine uptake by types I and II cells in rat lung slices. 206 Jun 7

The metabolism of biogenic amines by the filarial worm, Brugia pahangi, was investigated by incubating cut worms with radio-labelled amine substrates. Two-dimensional thin-layer chromatography and analysis on two high-performance liquid chromatography systems showed that [14C]5-hydroxytryptamine was metabolised to a less polar compound that was identified as N-acetyl 5-hydroxytryptamine. N-Acetyloctopamine and N-acetyldopamine were also formed when cut B. pahangi were incubated with [14C]octopamine and [3H]dopamine, respectively. N-Acetyltransferase activity towards 5-hydroxytryptamine was readily detected in nematode homogenates. This enzyme was localised in a 50,000 x g supernatant and required the addition of the co-substrate, acetyl CoA, for activity. No evidence was obtained for the involvement of monoamine oxidases in the metabolism of 5-HT in these filarial worms.
Mol Biochem Parasitol 1990 Dec
PMID:N-acetylation of serotonin, octopamine and dopamine by adult Brugia pahangi. 209 Sep 41

Platelet 5-hydroxytryptamine (5HT) uptake was measured in 12 healthy subjects in the spring, summer, and late autumn. The uptake was performed according to the method of Arora and Meltzer (1981). The maximal velocity of 5HT uptake was higher in the spring and in summer than in the autumn. In addition, a significant negative correlation between the Michaelis constant and the photoperiod was observed in spring. These findings seem to indicate the possible evidence of physiological season-related changes of platelet 5HT uptake that may be linked to the photoperiod.
Mol Chem Neuropathol
PMID:Seasonal serotonin uptake changes in healthy subjects. 209 81

1. Earlier reports from this and other laboratories have indicated that wide variations exist in estimates of the concentrations of norepinephrine in the brain and heart of the snail Helix aspersa. This is a report on investigations of norepinephrine concentrations in Helix aspersa tissues using high-performance liquid chromatography with electrochemical detection. In addition, the effects of treatment with some amino acid precursors or enzyme inhibitors on the concentrations of norepinephrine, dopamine, 5-hydroxytryptamine, and some of their metabolites were investigated. 2. The levels of norepinephrine in the brain were low (46 ng/g) in comparison to dopamine (2.1) micrograms/g) and 5-hydroxytryptamine (2.6 micrograms/g). Epinephrine was not observed in either snail heart of snail nervous tissue. 3. Administration of L-3,4-dihydroxyphenylalanine resulted in elevated snail brain dopamine, while 3,4-dihydroxyphenylserine treatment increased norepinephrine. Treatment with blockers of tyrosine hydroxylase and aromatic-L-amino acid decarboxylase reduced dopamine concentrations without affecting 5-hydroxytryptamine. 4. The dopamine metabolite 3,4-dihydroxyphenylacetic acid was observed only after administration of L-3,4-dihydroxyphenylalanine or dopamine and then only in very small amounts. At no time was the dopamine metabolite homovanillic acid or the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid observed in brain, heart, or whole-body extracts of the snail. 5. Incubation of nervous tissue with either dopamine or 5-hydroxytryptamine resulted in the production of electrochemically active metabolites which were identified by oxidation characteristics and cochromatography with synthesized standards as the gamma-glutamyl conjugates of the amines. Treatment of snails with 5-hydroxytryptamine or dopamine also resulted in the production of gamma-glutamyl conjugates. 6. The present experiments show that great care must be exercised when measuring monoamines and their metabolites in gastropod tissues by high-performance liquid chromatography with electrochemical detection.
Cell Mol Neurobiol 1990 Jun
PMID:High-performance liquid chromatographic analysis of monoamines and some of their gamma-glutamyl conjugates produced by the brain and other tissues of Helix aspersa (Gastropoda). 211 17


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