Regulation of Cyclic AMP Levels in Mammalian Retina: Effects of Depolarizing Agents and Transmitters

Cellular depolarization in brain results in a modulation of cAMP levels by releasing neurotransmitters having receptors linked via GTP-binding proteins to adenylate cyclase. In order to determine the transmitters regulating cAMP during cellular depolarization in mammalian retina, the modulation of cAMP by depolarizing media was investigated. Cyclic AMP levels in light adapted retinas increased following exposure to depolarizing media, but levels in dark adapted retinas remained unaltered. The depolarization-induced modulation of cAMP levels persisted in dystrophic retinas, suggesting that the response occurred in the inner retina. In microdissected discrete retinal layers from rabbit, levels of cAMP were increased following perfusion with depolarizing medium in the outer plexiform and inner nuclear layers, consistent with the observation seen with mouse retinas. To begin to identify transmitters released by cellular depolarization, a variety of transmitters and/or antagonists were included in the incubation medium. Haloperidol reduced the depolarization induced increase in cAMP levels by 25% in normal mouse retinas, and 75% in dystrophic retinas. Dopamine elevated cAMP levels in normal and dystrophic mouse retinas, and when combined with depolarizing medium, additive increases were observed. The effects of various neurotransmitters on retinal cAMP levels in the absence of any phosphodiesterase inhibitors were assessed, and both dopamine and norepinephrine were found to increase cAMP levels in normal and dystrophic retinas. Phentolamine antagonized the increase elicited by norepinephrine. When dopamine and norepinephrine were combined non-additive increases were observed. Serotonin, GABA, acetylcholine, histamine and adenosine had little or no significant effect on the retinal levels of cAMP in either normal or dystrophic mouse retinas. These results indicate that depolarizing media increase cAMP levels partially by releasing dopamine. The processes regulating cAMP levels in retina are both different and similar to those in brain.