Yonago Acta medica 1992;35:23–36

Reduction in Cyclic Adenosine 3',5'-Monophosphate Response to Dopamine in Retinas from Streptozotocin-Induced Diabetic Rats

Chiharu Okada*†, Yoshinori Kamisaki* and Tadao Itoh*

*Department of Clinical Pharmacology, and †Department of Ophthalmology, Faculty of Medicine, Tottori University, Yonago 683, Japan

The cyclic adenosine 3',5'-monophosphate (cAMP) response to dopamine was investigated in the retinas of diabetic rats, which were treated with strepeozotocin (60 mg/kg) 3 weeks before the experiment. In the diabetic retina, dopamine (100 µmol/L)-induced cAMP accumulation was significantly reduced to 65% of that in the normal retina. The effects of dopamine (100 µmol/L) were counteracted by SCH23390 (D_l-antagonist) in both diabetic and normal retinas, while sulpiride (D₂-antagonist) augmented the effects of dopamine with the same potency and efficacy in those retinas, suggesting that diabetes may damage the cAMP accumulation system through dopamine D_l receptors. There was no difference between the bindings of ¹²⁵I-SCH23982 to the dopamine D_l receptors in diabetic and normal retinal membranes. Forskolin (10 µmol/L)-stimulated adenylate cyclase activity was significantly higher in the diabetic retina than in the normal retina. When retinal membranes were incubated with 5'-guanylyl imidodiphosphate (10 µmol/L), the adenylate cyclase activity in the diabetic retina was significantly reduced to 63% of the activity in the normal retina. These findings suggest that streptozotocin-induced diabetes may cause a reduction in the retinal cAMP response to dopamine through dysfunction of stimulatory guanosine 5'-triphosphate-binding protein.

Key words: cyclic adenosine 3',5'-monophosphate; diabetes; dopamine; guanosine 5'-triphosphate-binding protein; retina

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