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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1997-12-31
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pubmed:abstractText |
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a metabolite of NADP, which can release Ca2+ from stores that are distinct from those activated by either cyclic ADP-ribose or inositol 1,4,5-trisphosphate (IP3). It has previously been suggested that thio-NADP is a specific antagonist of NAADP (Chini et al. [1995] J. Biol. Chem. 270, 3216-3223). Its effects in sea-urchin egg homogenates were investigated. At 50 microM, thio-NADP activates partial Ca2+ release and totally inhibits subsequent challenge with a saturating concentration of NAADP. Purification by HPLC eliminates the Ca2+ releasing activity of 50 microM thio-NADP and reduces the subsequent inhibition by 73.7 +/- 1.3%. The residual inhibitory effect is no more than that exerted by 50 microM of either NADP itself or nicotinic acid adenine dinucleotide (NAAD). These results are confirmed by 32P-NAADP binding studies. Unpurified thio-NADP inhibits the specific 32P-NAADP binding to egg microsomes with an IC50 of 40 microM. After HPLC purification, only 20% inhibition is seen at a concentration as high as 50 microM, similar to the extent of inhibition effected by 40 microM NADP. These results indicate the inhibitory substance in thio-NADP is a contaminant. The partial Ca2+ release activity of unpurified thio-NADP suggests the contaminant is NAADP itself. This is supported by the fact that pretreatment with a subthreshold concentration of only 2 nM NAADP totally desensitizes the egg homogenates such that no Ca2+ response is seen with saturating NAADP. Estimation from the binding studies shows that a contamination of 0.012% of NAADP in the unpurified thio-NADP samples is sufficient to account for the inhibitory effects. These results indicate thio-NADP is not an antagonist of NAADP.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Anion Exchange Resins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic ADP-Ribose,
http://linkedlifedata.com/resource/pubmed/chemical/Mono Q,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/NADP,
http://linkedlifedata.com/resource/pubmed/chemical/Resins, Synthetic,
http://linkedlifedata.com/resource/pubmed/chemical/nicotinic acid adenine dinucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/thionicotinamide adenine...
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pubmed:status |
MEDLINE
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pubmed:issn |
1085-9195
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
63-73
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9386893-Adenosine Diphosphate Ribose,
pubmed-meshheading:9386893-Animals,
pubmed-meshheading:9386893-Anion Exchange Resins,
pubmed-meshheading:9386893-Calcium,
pubmed-meshheading:9386893-Chromatography, High Pressure Liquid,
pubmed-meshheading:9386893-Chromatography, Ion Exchange,
pubmed-meshheading:9386893-Cyclic ADP-Ribose,
pubmed-meshheading:9386893-Drug Contamination,
pubmed-meshheading:9386893-NAD,
pubmed-meshheading:9386893-NADP,
pubmed-meshheading:9386893-Oocytes,
pubmed-meshheading:9386893-Resins, Synthetic,
pubmed-meshheading:9386893-Sea Urchins
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pubmed:year |
1998
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pubmed:articleTitle |
Thio-NADP is not an antagonist of NAADP.
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pubmed:affiliation |
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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