The uptake of 14C-chloroquine by mouse pancreatic islets in vitro

The uptake of 14C-chloroquine by isolated mouse pancreatic islets in vitro was investigated. The islets were found to have a very high capacity to accumulate the substance. The uptake of 14C-chloroquine in the islets was a saturable process. Metabolic inhibitors, ouabain, anaerobic conditions and absence of glucose did not inhibit the uptake of 14C-chloroquine in the islets, suggesting that the substance is accumulated by some means other than energy-dependent active transport or pinocytosis. The uptake of 14C-chloroquine was inhibited by low temperature and low pH and in the presence of mepacrine, chlorpromazine, imipramine and desmethylimipramine. Only a small part of the 14C-chloroquine which had been taken up in the islets left the cells during 45 min. incubation in non-radioactive media. Two possible mechanisms for the uptake of 14C-chloroquine in the islets are considered: (1) The accumulation may be due to a binding of the substance to cellular constituents. (2) Chloroquine may be trapped by protonation within lysosomes or other membrane-surrounded organelles with low pH.