Alteration of retinal choline metabolism in an experimental model for photoreceptor cell degeneration.
The choline analog hemicholinium-3 causes selective degeneration of the cones and rods in the rabbit retina. These experiments examine some biochemical effects of hemicholinium-3 on metabolic pathways involved in choline metabolism. No effect of the drug on several important photoreceptor biosynthetic functions was found: leucine incorporation into TCA-precipitable material, glycerol incorporation into phospholipids, and phosphatidylcholine formation by either base exchange or choline phosphotransferase activity. However, hemicholinium-3 does selectively affect free choline use: high-affinity uptake, phosphorylation and subsequent incorporation into lipid. In each instance, hemicholinium-3 causes a significant inhibition of control activity at a concentration of 30 microM, a dosage that causes complete photoreceptor outer segment degeneration in mammalian retinas. Thus, it seems that the enormous synthetic requirements for phosphatidylcholine leave the photoreceptor cell in fragile metabolic balance, and transient alteration of this balance may destroy the outer segment.
D000818:Animals; D002417:Cattle; D002794:Choline / Q000378:metabolism*; D005136:Eye Proteins / Q000096:biosynthesis; D005990:Glycerol / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D012162:Retinal Degeneration / Q000378:metabolism*
D005136:Eye Proteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D006426:Hemicholinium 3; D002794:Choline; D005990:Glycerol