Cadmium increases ( sup 3 H)inositol phosphate production and releases stored Ca sup 2+ : Evidence for a novel Ca sup 2+ -mobilizing receptor antagonized by zinc

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

OSTI ID:5471886

Dwyer, S D

Cadmium caused a spike in cytoplasmic free (Ca{sup +}) ((Ca{sup +}){sub i}) similarly to bradykinin in cultured human skin fibroblasts. Cadmium increased (Ca{sup 2+}){sub i} in the presence or absence of external Ca{sup 2+}. After bradykinin produced a spike in (Ca{sup 2+}){sub i}, the addition of cadmium had no effect on (Ca{sup 2+}){sub i} indicating that cadmium and bradykinin release Ca{sup 2+} from the same intracellular pool. Cadmium triggered a concentration-dependent increase in {sup 45}Ca{sup 2+} efflux. Half-maximal stimulation of efflux occurred at 0.1 {mu}M cadmium. Certain other metals also stimulated {sup 45}Ca{sup 2+} efflux. The potency order of the metals was Cd{sup 2+} > Co{sup 2+} > Ni{sup 2+} > Fe{sup 2+} > Mn{sup 2+}. Zn{sup 2+} competitively inhibited Cd-evoked {sup 45}Ca{sup 2+} efflux but had no effect on bradykinin-evoked efflux. Cadmium also decreased total cell Ca{sup 2+} by 50-60% within 2 min similarly to bradykinin. Decreasing external Na{sup +} from 120 mM to 3 mM caused a spike in (Ca{sup 2+}){sub i}, an 8-fold increase in {sup 45}Ca{sup 2+} efflux, and rapidly decreased total cell Ca{sup 2+} by 40% similarly to cadmium and bradykinin. Decreasing external pH also increased (Ca{sup 2+}){sub i}, stimulated {sup 45}Ca{sup 2+} efflux, and decreased total cell Ca{sup 2+}. The three unusual stimuli (cadmium, decreasing external Na{sup +}, and decreasing external pH) trigger rapid increases in ({sup 3}H) inositol 1,4,5-trisphosphate (IP{sub 3}), which indicates that IP{sub 3} is the intracellular messenger for release of stored Ca{sup 2+} by these three unusual stimuli. A single receptor appears to mediate the Ca{sup 2+} mobilizing response to all three stimuli.

• Research Organization: Alabama Univ., Birmingham, AL (United States)
• OSTI ID: 5471886
• 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.
59 BASIC BIOLOGICAL SCIENCES
CADMIUM
BIOLOGICAL EFFECTS
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
COBALT
IRON
MANGANESE
NICKEL
PHOSPHOLIPIDS
BIOSYNTHESIS
ZINC
CALCIUM 45
CATIONS
DOSE-RESPONSE RELATIONSHIPS
KININS
RECEPTORS
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CALCIUM ISOTOPES
CHARGED PARTICLES
DAYS LIVING RADIOISOTOPES
ELEMENTS
ESTERS
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
IONS
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
MEMBRANE PROTEINS
METALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
SYNTHESIS
TRANSITION ELEMENTS
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques