Further characterization of 5-HT1A receptors in the goldfish retina: role of cyclic AMP in the regulation of the in vitro outgrowth of retinal explants.
The presence of serotonin 5-HT1A receptors and their physiological role were further characterized in the goldfish retina. The effects of the 5-HT6/7 receptor antagonists pimozide, fluphenazine and amoxapine, the 5-HT1A receptor antagonist WAY-100,135, and the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, on the 5-HT1A receptor agonist [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes, were evaluated. In addition, the effects of serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin, WAY-100,135, the adenylate cyclase inhibitors SQ22536 and MDL12330A, and the cyclic AMP analog 8-bromoadenosine-3':5' cyclic monophosphate were also studied on neuritic outgrowth from retinal explants. WAY-100,135 but not 5-HT6/7 receptor antagonists inhibited [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding to retinal membranes N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline decreased [3H]8-hydroxy-2-(di-n-propylamino)tetralin binding sites up to 70%, while receptor turnover was similar to that reported in other tissues. Serotonin and 8-hydroxy-2-(di-n-propylamino)tetralin stimulated cyclic AMP production, both ex vivo and in vitro, and these increases were related to inhibition of neuritic outgrowth. The inhibitory effect was reduced by SQ22536 and by WAY-100,135, and was mimicked by 8-bromoadenosine-3':5'cyclic monophosphate. This study supports previous findings about the role of serotonin as a regulator of axonal outgrowth during in vitro regeneration of the goldfish retina and demonstrates that this effect is mediated, at least in part, by 5-HT1A receptors through a mechanism which involves an increase of cyclic AMP levels.
Schmeer
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Laboratorio de Neuroquímica, Centro de Biofisica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
Obregón
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Urbina
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Lima
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006054:Goldfish; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D010879:Piperazines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014316:Tritium
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D007097:Imines; D010879:Piperazines; D011804:Quinolines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014316:Tritium; C081293:WAY 100135; C017759:9-(tetrahydro-2-furyl)-adenine; C000470:EEDQ; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C014925:RMI 12330A; D000242:Cyclic AMP; D000225:Adenine