Characterization of the activation of Na/sup +//H/sup +/ exchange in lymphocytes by phorbol esters: change in cytoplasmic pH dependence of the antiport

Journal Article · Fri Mar 01 04:00:00 EST 1985 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.82.5.1429· OSTI ID:5607053

Grinstein, S; Cohen, S; Geotz, J D; Rothstein, A; Gelfand, E W

Phorbol 12-myristate 13-acetate and other phorbol esters induce an intracellular alkalinization in rat thymic lymphocytes. An extracellular acidification can be recorded concomitantly. This transmembrane H/sup +/ (equivalent) flux is dependent on external Na/sup +/ and is amiloride sensitive. Phorbol esters also stimulate an amiloride-sensitive uptake of /sup 22/Na/sup +/, suggesting activation of Na/sub 0//sup +//H/sub i//sup +/ exchange. Only those phorbol derivatives that are tumor promoters and activators of protein kinase C stimulate the antiport. Activation of the Na/sup +//H/sup +/ exchange is brought about by a change in the cytoplasmic pH sensitivity of the antiport. Activation of the Na/sup +//H/sup +/ exchanger by phorbol esters results in membrane hyperpolarization, due to indirect stimulation of the electrogenic Na/sup +//K/sup +/ pump by the increased intracellular Na/sup +/ concentrations. Increased Na/sup +//H/sup +/ exchange also produces cell swelling, which may be one of the earliest manifestations of the growth-promoting properties of the phorbol esters.

• Research Organization: Univ. of Toronto, Ontario
• OSTI ID: 5607053
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:5; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARCINOGENS
CATIONS
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
CHEMISTRY
CONNECTIVE TISSUE CELLS
CYTOPLASM
ENZYMES
ESTERS
HYDROGEN COMPOUNDS
INJURIES
ION EXCHANGE
IONS
LEUKOCYTES
LYMPHATIC SYSTEM
LYMPHOCYTES
MAMMALS
MATERIALS
MEMBRANE TRANSPORT
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PH VALUE
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROMOTERS
RATS
RODENTS
SODIUM COMPOUNDS
SOMATIC CELLS
THYMUS
TOXICITY
TRANSFERASES
TUMOR PROMOTERS
VERTEBRATES