Role of intracellular pH in ligand internalization
Internalization of EGF and transferrin measured as the rate of uptake of /sup 125/I-labeled ligands was compared in the cell line CCL39 and a mutant derivative, PS120, lacking the Na/sup +//H/sup +/ antiport system. No significant alteration was detected between the two cell lines. In contrast, pretreatment of the mutant cells PS-120 with 20 mM NH/sub 4/Cl for 30 min to decrease persistently intracellular pH resulted in an increase in /sup 125/I-EGF and /sup 125/I-transferrin uptake by 60% and 25%, respectively. However, similar NH/sub 4/Cl pretreatment of the parental cell line, CCL-39, which only affected intracellular pH very transiently did not cause an increase of ligand uptake. The binding of /sup 125/I-EGF to CCL-39 and PS-120 cells with or without NH/sub 4/Cl pretreatment showed that NH/sub 4/Cl pretreatment did not affect EGF binding in either CCL-39 or PS-120 cells. Since cells regulate intracellular pH by ion transport systems, we also examined the role of Na/sup +/, K/sup +/ -ATPase. Ouabain, an inhibitor of Na/sup +/, K/sup +/ -ATPases, showed no effect on /sup 125/I-EGF uptake in either of the cell types with or without NH/sub 4/Cl pretreatment. Taken together, these results suggest that the plasma membrane-bound Na/sup +//H/sup +/ antiport, a major pH/sub i/-regulating system in vertebrates, indirectly plays a role in ligand internalization through regulation of intracellular pH.
- Research Organization:
- National Institutes of Health, Bethesda, MD
- OSTI ID:
- 6942636
- Journal Information:
- J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 128:1; ISSN JCLLA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMMONIUM CHLORIDES
AMMONIUM COMPOUNDS
AMMONIUM HALIDES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CHLORIDES
CHLORINE COMPOUNDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
FIBROBLASTS
GLOBULINS
GLOBULINS-BETA
GROWTH
HALIDES
HALOGEN COMPOUNDS
HAMSTERS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGANDS
LUNGS
MAMMALS
MEMBRANE TRANSPORT
METALLOPROTEINS
MUTANTS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PH VALUE
PHYSIOLOGY
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
TRANSFERRIN
UPTAKE
VERTEBRATES