Increased Levels of 3′,5′‐Cyclic Adenosine Monophosphate Induced by Cobaltous Ion or 3‐Isobutylmethylxanthine in the Incubated Mouse Retina: Evidence Concerning Location and Response to Ions and Light

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Abstract
Dark levels of 3′,5′-cyclic adenosine monophosphate (cyclic AMP) of mouse retinas incubated in Earle's medium were elevated by 3-isobutylmethylxanthine (IBMX) and/or Co2+ or Mn2+, but not by Cd2+, methylverapamil, or excess Mg2+ or Ca2+. Light reduced elevated dark levels of cyclic AMP in the presence of agents known to block the light modulation of postreceptoral neurons (aspartate, Co2+ high Mg2+), a finding consistent with a cyclic AMP metabolism in photoreceptors. Co2+-elevated cyclic AMP levels were not less light-sensitive than cyclic GMP levels. Ouabain substantially increased IBMX-elevated cyclic AMP with a persistent light response, but reduced the dark action of Co2+. IBMX, but not Co2+, also increased cyclic AMP in receptorless (rd/rd) retinas; haloperidol partly reduced this IBMX effect. In normal retinas in Co2+ medium, progressively replacing Na+ by K+ (but not choline+) from 1–50 mm caused a progressive fall in dark, light-sensitive cyclic AMP levels, but from 50 to 100 mm-K+ there appeared haloperidol-preventable increases in both the dark- and light-insensitive levels of cyclic AMP. In IBMX-aspartate medium a haloperidol-preventable, light-insensitive increase in cyclic AMP appeared from 20 mm-K+ upwards. Haloperidol-preventable increases in cyclic AMP as induced by high K+ required Co2+ in normal retinas, but not in receptorless retinas, and 5 mm-Co2+ greatly increased the response to dopamine in receptorless retinas. The postdopaminergic neurons, which are 4th-order neurons, may have become hyper-sensitive to dopamine in receptorless retinas consequent to the absent signal from the 1st-order photoreceptors, or directly, as an effect of the same gene underlying the dystrophy.