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.
Dark levels of 3',5'-cyclic adenosine monophosphate (cyclic AMP) of mouse retinas incubated in Earle's medium were elevated by 3-isobutyl-methylxanthine (IBMX) and/or Co2+ or Mn2+, but not by Cd2+, methylverapamil, or excess Mg2+ of Ca2+. Light reduced elevated dark levels of cyclic AMP in the presence of agents known to block the light modulation of post-receptoral 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 nM-Co2+ greatly increased the response to dopamine in receptorless retinas. The post-dopaminergic neurons, which are 4th-order neurons, may have become hypersensitive 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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D003624:Darkness; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D010042:Ouabain / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives*
D001224:Aspartic Acid; D003035:Cobalt; D004533:Egtazic Acid; D010042:Ouabain; D013806:Theophylline; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine