Binding of chlorpromazine to cultured retinal pigment epithelial cells loaded with melanin.
The accumulation of chlorpromazine (CPZ) in cultured bovine amelanotic retinal pigment epithelial (RPE) cells artificially loaded with melanin was investigated. The melanin was isolated from human eye bank eyes. Suspensions of the melanin were added to the RPE cells and incubated for 3 hrs. The cells ingested the melanin which was dispersed in the cytoplasm of the cells. They were not adhering to the cell membrane. The melanin-loaded cells grew in culture, although their rate of growth was slower than that of the control RPE cells not loaded with melanin. When the melanin-loaded cells were treated with CPZ, these cells accumulated a greater amount of CPZ than the control cells. A greater amount of CPZ was released from the melanin-loaded cells than from the control cells. The results suggest that some drugs or chemicals such as CPZ could accumulate in vivo in larger quantities and for longer periods in melanotic cells than in nonmelanotic cells. These compounds may subsequently be released into the extracellular fluid, thus affecting the neighbouring cells. This phenomenon may play an important role in the activities of these drugs in the melanotic cells and in the cells adjacent to the melanotic cells. These results suggested that cultured cells loaded with melanin could be used as a suitable model for studying the mechanisms of binding of drugs to intracellular melanin, and of their subsequent release outside the cells.
Basu
P K
PK
Department of Ophthalmology, University of Toronto, Canada.
Menon
I A
IA
Persad
S D
SD
Wiltshire
J D
JD
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008543:Melanins / Q000008:administration & dosage / Q000378:metabolism*; D010587:Phagocytosis; D010857:Pigment Epithelium of Eye / Q000378:metabolism*
D008543:Melanins; D002746:Chlorpromazine