Dopamine and its agonists reduce a light-sensitive pool of cyclic AMP in mouse photoreceptors.
The exposure to bright light of dark-adapted (DKA) mouse retinas incubated in the dark (DI) in IBMX-containing medium causes a marked loss of cyclic AMP. This light response also occurs if the medium contains 10 mM aspartate or cobaltous ion, agents believed to confine the effects of light to photoreceptors. Thus, the action of light in the presence of either of these agents defines a light-sensitive pool of cyclic AMP in photoreceptors. This pool could also be reduced or eliminated in DKA-DI retinas by nanomolar to micromolar levels of dopamine (if the medium contained SCH23390, a potent antagonist of D1 receptors), thus indicating an agonistic action of dopamine at D2 receptors. The D2 agonists LY171555 (EC50 10 nM) or (+)-3-PPP also reduced the cyclic AMP level in the dark. Of the D2 antagonists tested, the butyrophenone spiperone (in the presence of the 5HT-2 blocker ketanserin) countered the action of the D2 agonists but substituted benzamides were ineffective. Consistently, the D2 agonists had no effect on cyclic AMP levels of mutant retinas lacking photoreceptors (rd/rd), but reduced cyclic AMP in DKA-DI glutamate-modified retinas which exhibit a major loss of inner retinal neurons without apparent loss of photoreceptors. The D1 antagonist SCH23390 only reduced cyclic AMP levels of DKA-DI retinas when cyclic AMP levels had been elevated by adding dopamine to the incubation medium.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
A I
AI
Cohen
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Blazynski
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003623:Dark Adaptation; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D008024:Ligands; D008027:Light; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000378:metabolism
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D008024:Ligands; D010880:Piperidines; D011954:Receptors, Dopamine; D019257:Quinpirole; C026539:preclamol; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine