Carbomoylation of Proteins Following Administration to Rats of Carbamoyl Phosphate and Cyanate and Effects on Memory.

Both [¹⁴C]carbamoyl phosphate and sodium [¹⁴C]cyanate injected in rats were extensively incorporated into blood proteins, red cells and tissues, including brain. The rate of cyanate binding to blood protein plateaus 4 h after intraperitoneal administration of [¹⁴C]cyanate. The rapid disappearance of free [¹⁴C]cyanate was shown to be largely due to protein binding and the release of ¹⁴CO₂ was found to decrease sharply at 4 h when cyanate binding is essentially complete. Retention of carbamoylated proteins was measured after injection of [¹⁴C]cyanate, and at 110 days, when bound radioactivity in blood protein was negligible, brain protein retained about 50% of the radioactivity found at 6 h. A dose-related decrease m learning ability was observed when rats injected with 50, 100 and 150 µmol cyanate per day were tested in a Lashley maze No. III filled with water. This retardation persisted when the animals were reused nine weeks after termination of cyanate injection. When retested at eight months, no retardation could be demonstrated. At this time, only 10% modified proteins should remain in the brain according to the data presented on retention of carbamoylated proteins. The application of this data to a biochemical model for learning based on synaptic facilitation by modified proteins is discussed, as well as the implied effect on humans treated for sickle-cell disease by administration of cyanate or carbamoyl phosphate. [ABSTRACT FROM AUTHOR]