Analysis of pre- and postsynaptic factors of the serotonin system in rabbit retina.

Mitchell, Cheryl K.; Redburn, Dianna A.

doi:10.1083/jcb.100.1.64

Cited by 49 publications

(40 citation statements)

References 18 publications

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“…114 Serotonin also inhibits the release of thyrotropin releasing hormone from rat retinas. 115 5-HT 1 receptors are present on rabbit retinal membranes, 92 and mRNA for 5-HT 1A is present in rabbit and rat retinas. 116,117 The effects of the 5-HT 1A agonist 8-hydroxy-2-(di-npropylamino) tetralin(8-OH-DPAT) are particularly well-characterized in rabbit retinas.…”

Section: Retinopetal Axons Containing Serotoninmentioning

confidence: 99%

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Retinopetal Axons in Mammals: Emphasis on Histamine and Serotonin

Gastinger

Tian

Horváth

et al. 2006

Current Eye Research

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Since 1892, anatomical studies have demonstrated that the retinas of mammals, including humans, receive input from the brain via axons emerging from the optic nerve. There are only a small number of these retinopetal axons, but their branches in the inner retina are very extensive. More recently, the neurons in the brain stem that give rise to these axons have been localized, and their neurotransmitters have been identified. One set of retinopetal axons arises from perikarya in the posterior hypothalamus and uses histamine, and the other arises from perikarya in the dorsal raphe and uses serotonin. These serotonergic and histaminergic neurons are not specialized to supply the retina; rather, they are a subset of the neurons that project via collaterals to many other targets in the central nervous system, as well. They are components of the ascending arousal system, firing most rapidly when the animal is awake and active. The contributions of these retinopetal axons to vision may be predicted from the known effects of serotonin and histamine on retinal neurons. There is also evidence suggesting that retinopetal axons play a role in the etiology of retinal diseases. Keywordscentrifugal; efferent; histamine; primate; serotonin MORPHOLOGY AND FUNCTIONS OF RETINOPETAL AXONS IN MAMMALSIn mammalian retinas, three types of retinopetal axons have been distinguished by morphological criteria. The first type gives rise to terminals in the outer strata of the inner plexiform layer (IPL). Typically, the axons terminate along the border with the inner nuclear Copyright (Figs. 1A and 1C). Using the Golgi method, axons with this pattern of branching have been identified in dog 1 and chimpanzee 2 retinas. The second type of retinopetal axon is larger in diameter, varicose, and terminates in the outer plexiform layer (OPL). In rats, these axons are labeled with antibodies to serotonin after loading the retina with a related indoleamine, 5,7-dihydroxytryptamine (5,7-DHT). They originate from perikarya in the optic chiasm or the preoptic area of the hypothalamus. 3 Retinopetal axons similar to these are labeled with neurofilament antibodies in the mouse retina. 4 Neurons that project from the anterior hypothalamus to the retina have been identified in a prosimian, 5 but their terminals in the retina have not been described.The third type of retinopetal axon branches extensively in IPL (Fig. 1B). Using the Golgi method, Polyak described axons like these in macaque retinas. 2 They run in the optic fiber layer (OFL), and they give off a nearly vertical branch to the IPL, where they branch extensively in a broad band in the center of the layer. In the mouse retina, axons with a similar branching pattern are labeled with neurofilament antibodies. 4 These axons are also labeled using reduced silver stains in monkey 6,7 and human 8,9 retinas. These studies confirmed and extended Polyak's descriptions, and they also demonstrated clear morphological differences between retinopetal axons and those of ganglion cells with intraretin...

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Section: Retinopetal Axons Containing Serotoninmentioning

confidence: 99%

“…[89][90][91][92][93] These low levels of endogenous serotonin suggest that serotonin is used as a neurotransmitter by a sparse population of retinopetal axons rather than amacrine cells. Serotonin is synthesized from tryptophan in two steps by tryptophan hydroxylase and amino acid decarboxylase.…”

Section: Retinopetal Axons Containing Serotoninmentioning

confidence: 99%

Retinopetal Axons in Mammals: Emphasis on Histamine and Serotonin

Gastinger

Tian

Horváth

et al. 2006

Current Eye Research

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“…Serotonin (5-hydroxytryptamine, 5-HT) has been reported to be present in the retina of several vertebrates (9)(10)(11). The existence of the specific uptake systems for 5-HT or a closely related indoleamine in the vertebrate retinas suggested that indoleamines are taken up and released for neurotransmission.…”

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confidence: 99%

Morphological characterization and distribution of indoleamine-accumulating cells in the rat retina.

Matsumoto

Ueda

Kawata

1992

Acta Histochem. Cytochem

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Rat retina, which was intravitreously injected with 5-hydroxytryptamine (5-HT) or 5-hydroxytryptophane (5-HTP), was examined to identify indoleamine-accumulating cells by an immunohistochemical method in a flat-mount view and transverse sections. In the retina treated with 5-HT the immunostaining was observed in the cell processes, while in the retina treated with 5-HTP a large number of the immunoreactive cells with processes were noticeable. According to their morphological features and locations, they were divided into 5 types. Type 1 cells were large ovoid with a few processes and located in the inner lamina of the inner nuclear layer (INL). The majority of their processes ramified in the interface between the INL and inner plexiform layer (IPL). Type 2 and type 3 cells had large ovoid cell bodies, and the former was located in the ganglion cell layer (GCL) but the latter was placed in the IPL. Type 4 cells had small round cell bodies with a few fine processes and were placed in the inner lamina of the INL. Type 5 cells had the same features as type 4 cells but were displaced in the GCL.These immunoreactive indoleamine-accumulating cells are categorized as amacrine cells from their shape and location. A morphological variety of indoleamine-accumulating cells in the rat retina indicates a wide range of involvement of amacrine cells in the signal transmission of visual information.

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“…This system is characterized by ligand specificity, Na+ and temperature dependence, antagonizability by known blockers (nortriptyline, imipramine, and desipramine), and saturable and high-affinity uptake kinetics. In particular, the Km and Vma values are well within the range of such parameters measured for 5-HT-uptake systems in the central nervous system and blood platelets (6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 79%

“…Although the physiology and pharmacology of a number of neurotransmitter transport systems including that for serotonin have been extensively studied (6)(7)(8)(9)(10)(11)(12)(13), little is known about the biochemistry and molecular biology of any of these systems. With the hope of attaining such information, we report here the use of gene transfer (14)(15)(16)(17) in the establishment and identification of a clonal mouse fibroblast cell line, L-S1, that stably expresses a presumptively human highaffinity uptake system for serotonin (5-HT).…”

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confidence: 99%

Characterization of a genetically reconstituted high-affinity system for serotonin transport.

Chang¹,

Frnka²,

Chen³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identified several clonal cell lines that stably express a high-affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-[3H]HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high-affinity 5-HT uptake; (ii) both Nal and temperature dependences; (iv) kinetic saturability; and (v) high affinity for 5-HT (Km = 0.39 + 0. 10 jIM; V.. = 2.14 ± 0.55 pmol/min per mg of protein). This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, we postulate that the observed 5-HT-uptake system resulted from the expression of human gene(s) coding for the 5-HT transporter. Thus, cell lines such as L-S1 may represent novel means for screening and developing therapeutic agents specific for neurotransmitteruptake systems as well as substrates for the cloning and elucidation of the genes encoding the various neurotransmitter transporters.Inactivation of neurotransmitters, following their stimulated release into the synaptic cleft, is a key regulatory process in neurotransmission. For biogenic amine and amino acid neurotransmitters, the inactivation process is achieved mainly via transmitter-specific high-affinity transport systems present in the presynaptic neuron and/or surrounding glial cells (1-6). These transport mechanisms are also of significant clinical interest because some of their inhibitors are therapeutic agents for certain neurological disorders.Although the physiology and pharmacology of a number of neurotransmitter transport systems including that for serotonin have been extensively studied (6-13), little is known about the biochemistry and molecular biology of any of these systems. With the hope of attaining such information, we report here the use of gene transfer (14-17) in the establishment and identification of a clonal mouse fibroblast cell line, L-S1, that stably expresses a presumptively human highaffinity uptake system for serotonin (5-HT). MATERIALS AND METHODSTransfection of L-M Fibroblasts. Mouse L-M fibroblast cells (ATCC CCL 1.2) were plated in 100-mm culture dishes so that by the time of transfection the cell number would be about 106. Human genomic DNA and pSV2-neo, a plasmid bearing neomycin-resistance as a selectable marker (18), were cotransfected essentially by the method of calcium phosphate precipitation (19). After transfection, the cells were trypsinized and plated into 96-well plates. Selection of resistance to G418 (GIBCO; 400 tkg/ml) was maintained until transfectant colonies (typically three to five per well) were well established. Each well was then assayed for 5-[3H]HT uptake activities.Identificatio...

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Analysis of pre- and postsynaptic factors of the serotonin system in rabbit retina.

Cited by 49 publications

References 18 publications

Retinopetal Axons in Mammals: Emphasis on Histamine and Serotonin

Retinopetal Axons in Mammals: Emphasis on Histamine and Serotonin

Morphological characterization and distribution of indoleamine-accumulating cells in the rat retina.

Characterization of a genetically reconstituted high-affinity system for serotonin transport.

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