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
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
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CADMIUM
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CATIONS
CHARGED PARTICLES
COBALT
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ESTERS
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
IONS
IRON
ISOTOPE APPLICATIONS
ISOTOPES
KININS
LIPIDS
MANGANESE
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
METALS
NICKEL
NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDES
PHOSPHOLIPIDS
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RECEPTORS
SYNTHESIS
TRACER TECHNIQUES
TRANSITION ELEMENTS
ZINC