The effects of a whole series of adenine nucleotides on Ins(1,4,5)P3-induced Ca2+ release were characterized in permeabilized A7r5 smooth-muscle cells. Several adenine nucleotides activated the Ins(1,4,5)P3 receptor. It was observed that 3′-phosphoadenosine 5′-phosphosulphate, CoA, di(adenosine-5′)tetraphosphate (Ap4A) and di(adenosine-5′)pentaphosphate (Ap5A) were more effective than ATP. Ap4A and Ap5A also interacted with a lower EC50 than ATP. In order to find out how these adenine nucleotides affected Ins(1,4,5)P3-induced Ca2+ release, we have measured their effect on the response of permeabilized A7r5 cells to a progressively increasing Ins(1,4,5)P3 concentration. Stimulatory ATP and Ap5A concentrations had no effect on the threshold Ins(1,4,5)P3 concentration for initiating Ca2+ release, but they stimulated Ca2+ release in the presence of supra-threshold Ins(1,4,5)P3 concentrations by increasing the co-operativity of the release process. Inhibition of the Ins(1,4,5)P3-induced Ca2+ release at higher ATP concentrations was associated with a further increase in co-operativity and also with a shift in threshold towards higher Ins(1,4,5)P3 concentrations. ATP had no effect on the non-specific Ca2+ leak in the absence of Ins(1,4,5)P3. We conclude that the adenine-nucleotide-binding site can be activated by many different adenine nucleotides. Binding of these compounds to the transducing domain of the Ins(1,4,5)P3 receptor increases the efficiency of transmitting Ins(1,4,5)P3 binding to channel opening. The inhibition by high ATP concentrations is exerted at a different site, related to Ins(1,4,5)P3 binding.
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Research Article|
August 01 1997
Effect of adenine nucleotides on myo-inositol-1,4,5-trisphosphate-induced calcium release
Ludwig MISSIAEN;
Ludwig MISSIAEN
*
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
*To whom correspondence should be addressed.
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Jan B. PARYS;
Jan B. PARYS
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Humbert DE SMEDT;
Humbert DE SMEDT
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Ilse SIENAERT;
Ilse SIENAERT
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Henk SIPMA;
Henk SIPMA
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Sara VANLINGEN;
Sara VANLINGEN
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Karlien MAES;
Karlien MAES
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Rik CASTEELS
Rik CASTEELS
1Laboratorium voor Fysiologie, K.U. Leuven Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium
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Publisher: Portland Press Ltd
Received:
January 20 1997
Revision Received:
March 19 1997
Accepted:
March 27 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 325 (3): 661–666.
Article history
Received:
January 20 1997
Revision Received:
March 19 1997
Accepted:
March 27 1997
Citation
Ludwig MISSIAEN, Jan B. PARYS, Humbert DE SMEDT, Ilse SIENAERT, Henk SIPMA, Sara VANLINGEN, Karlien MAES, Rik CASTEELS; Effect of adenine nucleotides on myo-inositol-1,4,5-trisphosphate-induced calcium release. Biochem J 1 August 1997; 325 (3): 661–666. doi: https://doi.org/10.1042/bj3250661
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