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 wer e further characterized in the goldfish retina. The effects of the 5-HT6/7 receptor antagonists pimozide, fluphenazine and amoxapine, the 5-HT1A recep tor antagonist WAY-100,135, and the alkylating agent N-ethoxycarbonyl-2-eth oxy-1,2-dihydroquinoline, on the 5-HT1A receptor agonist [H-3]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 t he cyclic AMP analog 8-bromoadenosine-3 ' :5 ' cyclic monophosphate were al so studied on neuritic Outgrowth from retinal explants. WAY-100,135 but not 5-HT(6/7)receptor antagonists inhibited [H-3]8-hydroxy-2-(di-n-propylamino )tetralin binding to retinal membranes N-ethoxycarbonyl-2-ethoxy-1,2-dihydr oquinoline decreased [H-3]8-hydroxy-2-(di-n-propylamino)tetralin binding si tes up to 70%, while receptor turnover was similar to that reported in othe r 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 redu ced 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 regen eration of the goldfish retina and demonstrates that this effect is mediate d, at least in part, by 5-HT1A receptors through a mechanism which involves an increase of cyclic AMP levels.