Adenylate Cyclases in Vertebrate Retina: Enzymatic Characteristics in Normal and Dystrophic Mouse Retina

Abstract

Adenylate cyclase activity and the effects of various activators and inhibitors of this enzyme were measured in retinas from normal mice (C57BL/6J) and congenic animals with photoreceptor dystrophy. In normal retina, .apprx. 250 .mu.M-ATP was required for half-maximal stimulation of the enzyme. Activity was supported by Mg2+ and Mn2+, but Ca2+ was ineffective. The enzyme was inhibited by EGTA [ethyleneglycol-bis-(.beta.-aminoethylether)-N,N''-tetraacetic acid] and stimulated by 5''-guanylylimidodiphosphate (GPP(NH)P), dopamine and NaF. The stimulatory effects of GPP(NH)P and dopamine were greater in the presence of EGTA. Examination of microdissected normal retinas revealed that the inner (neural) retina had adenylate cyclase activity 4 times that of the photoreceptor cell layers, and that EGTA inhibited activity in the inner retina, but had no effect in the outer retina. In dystrophic retinas basal enzyme activity was 60% higher than that in normal retina. The enzyme in this tissue was stimulated by EGTA, GPP(NH)P and dopamine, and their effects were additive. Apparently adenylate cyclase activity in vertebrate retina is under complex regulation by substrate, divalent cations, guanine nucleotides, dopamine and perhaps calmodulin. Adenylate cyclase may not be evenly distributed in the retina and may be regulated differently in the inner and outer retina. Regulation of this enzyme in dystrophic retina may qualitatively and quantitatively differ from that in normal retina.