Publication Date:
1988-04-29
Description:
The kinetics of calcium release by inositol 1,4,5-trisphosphate (IP3) in permeabilized rat basophilic leukemia cells were studied to obtain insight into the molecular mechanism of action of this intracellular messenger of the phosphoinositide cascade. Calcium release from intracellular storage sites was monitored with fura-2, a fluorescent indicator. The dependence of the rate of calcium release on the concentration of added IP3 in the 4 to 40 nM range showed that channel opening requires the binding of at least three molecules of IP3. Channel opening occurred in the absence of added adenosine triphosphate, indicating that IP3 acts directly on the channel or on a protein that gates it. The channels were opened by IP3 in less than 4 seconds. The highly cooperative opening of calcium channels by nanomolar concentrations of IP3 enables cells to detect and amplify very small changes in the concentration of this messenger in response to hormonal, sensory, and growth control stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyer, T -- Holowka, D -- Stryer, L -- AI22449/AI/NIAID NIH HHS/ -- GM24032/GM/NIGMS NIH HHS/ -- GM30387/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1988 Apr 29;240(4852):653-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Sherman Fairchild Center, Stanford University School of Medicine, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2452482" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basophils
;
Benzofurans
;
Calcimycin/pharmacology
;
Calcium/*metabolism
;
Cell Membrane Permeability
;
Cytoplasm/metabolism
;
Fluorescent Dyes
;
Fura-2
;
Inositol 1,4,5-Trisphosphate
;
Inositol Phosphates/metabolism/*pharmacology
;
Ion Channels/drug effects/*metabolism
;
Kinetics
;
Leukemia, Experimental/metabolism
;
Rats
;
Spectrometry, Fluorescence
;
Sugar Phosphates/*pharmacology
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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