Intracellular pH: Its role in normal development and teratogenesis

Miscellaneous · Sun Jan 01 00:00:00 EST 1989

OSTI ID:5611412

Duggan, C A

Reduction of intracellular pH (pH{sub i}) leading to reduced cell proliferation has been proposed as a mechanism by which acetazolamide induces its teratogenic postaxial limb reduction defect in rodents. In vivo studies measured pH{sub i} using a weak acid and found that pH{sub i} decreased with increasing gestational age during the period of organogenesis in C57 mouse embryos. This decreasing pH{sub i} had a high correlation with the simultaneously occurring decrease in the rate of proliferation determined by {sup 3}H-thymidine incorporation. pH{sub i} or pH was measured for the embryo, embryonic plasma, and extraembryonic fluids following a teratogenic dose of acetazolamide in sensitive C57 and resistant SWV mice. Reduced embryonic pH{sub i} was seen only in the sensitive strain while both strains showed decreased pH values for embryo plasma and extraembryonic fluids, with larger reductions found in the C57 strain. The plasma membrane Na{sup +}/H{sup +} antiporter is known to regulate intracellular pH. Treatment with acetazolamide plus amiloride, and inhibitor of the Na{sup +}/H{sup +} antiporter, resulted in a dramatically increased teratogenic response in C57 embryos and several incidences of the specific limb defect in the resistant SWV embryos. The pH{sub i} and pH effects following the combined drug treatment resulted in larger reductions, the magnitude and duration being greatest in the sensitive strain. The presence of a functional Na{sup +}/H{sup +} antiporter in primary cultures of limb bud mesenchymal cells was documented for both strains of mice using a pH sensitive fluorescent dye. Quantitative studies were done to look for functional differences in the Na{sup +}/H{sup +} antiporter of limb cells from acetazolamide sensitive and resistant embryos.

• Research Organization: Cincinnati Univ., OH (United States)
• OSTI ID: 5611412
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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AMIDES
TERATOGENESIS
EMBRYONIC CELLS
CELL PROLIFERATION
CELL MEMBRANES
MICE
PH VALUE
PROTONS
SODIUM 22
SODIUM COMPOUNDS
TRACER TECHNIQUES
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
BARYONS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CELL CONSTITUENTS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANES
NANOSEC LIVING RADIOISOTOPES
NUCLEI
NUCLEONS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RADIOISOTOPES
RODENTS
SODIUM ISOTOPES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
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