Action of cholera toxin in the intestinal epithelial cells
The primary event in the action of cholera toxin on the isolated chick intestinal epithelial cell is its interaction with a large number of high affinity binding sites in the cell membrane. Binding of /sup 125/I-labeled toxin is rapid, temperature-dependent, reversible, and saturable over a wide range of concentrations and includes only a small contribution from nonspecific sites. A characteristic lag phase of 10 min occurs following the complete binding of toxin before any increase in cellular cAMP levels can be detected. The response (elevation of cellular cAMP) is linear with time for 40 to 50 min and causes a six- to eight-fold increase over control levels (10 to 15 picomole cAMP/mg cellular protein) at steady state. cAMP and agents that increase cAMP production inhibit Cl/sup -/-independent Na/sup +/ influx into the isolated enterocytes whereas chlorpromazine (CPZ) which completely abolishes toxin-induced elevation of cAMP both reverses and prevents the cAMP-mediated inhibition of Na/sup +/ entry. Correlation between cellular cAMP levels and the magnitude of Na/sup +/ influx provides evidence for a cAMP-mediated control of intestinal Na/sup +/ uptake, which may represent the mechanistic basis for the antiabsorptive effect of CT on Na/sup +/ during induction of intestinal secretion. The effect of cAMP on Na/sup +/ but not Cl/sup -/ influx preparations can be partially explained in terms of a cAMP-regulated Na/sup +//H/sup +/ neutral exchange system. Data on the coupling relationship between Na/sup +/ transport and the intra- and extracellular pH in the enterocytes show that an amiloride-sensitive electroneutral Na/sup +//H/sup +/ exchange process occurs. This coupling between Na/sup +/ and H/sup +/ is partially inhibited by CT and dbcAMP, suggesting that the Na/sup +//H/sup +/ exchange may be a cAMP-regulated process. 31 references, 32 figures, 5 tables.
- Research Organization:
- Rochester Univ., NY (USA)
- DOE Contract Number:
- AC02-76EV03490
- OSTI ID:
- 6538673
- Report Number(s):
- DOE/EV/03490-2264; ON: DE84016251
- Resource Relation:
- Other Information: Portions are illegible in microfiche products. Thesis
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CHOLERA
TOXICITY
TOXINS
BIOCHEMICAL REACTION KINETICS
AMP
ANIMAL CELLS
CATIONS
CELL CULTURES
CHLORIDES
EPITHELIUM
EXPERIMENTAL DATA
INTESTINES
IODINE 125
MEMBRANE TRANSPORT
SODIUM
TIME DEPENDENCE
TRACER TECHNIQUES
ALKALI METALS
ANIMAL TISSUES
ANTIGENS
BACTERIAL DISEASES
BETA DECAY RADIOISOTOPES
BODY
CHARGED PARTICLES
CHLORINE COMPOUNDS
DATA
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
GASTROINTESTINAL TRACT
HALIDES
HALOGEN COMPOUNDS
INFECTIOUS DISEASES
INFORMATION
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
IONS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MATERIALS
METALS
NUCLEI
NUCLEOTIDES
NUMERICAL DATA
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
REACTION KINETICS
TISSUES
TOXIC MATERIALS
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550901 - Pathology- Tracer Techniques