Ins(2,4,5)P3, a metabolically stable analogue of Ins(1,4,5)P3, is widely used in analyses of Ca2+ signalling pathways, but its utility depends upon it faithfully mimicking the effects of the natural messenger, Ins(1,4,5)P3, at InsP3 receptors. To compare the kinetics of InsP3-evoked 45Ca2+ mobilization, Ins(1,4,5)P3- and Ins(2,4,5)P3-stimulated 45Ca2+ release from the intracellular stores of permeabilized rat hepatocytes was measured using rapid superfusion. Both Ins(1,4,5)P3 and Ins(2,4,5)P3 caused concentration-dependent increases in the rate of 45Ca2+ efflux, which accelerated towards a peak and then abruptly switched to a bi-exponentially decaying release rate. However, the peak rate of 45Ca2+ mobilization evoked by maximal concentrations of Ins(2,4,5)P3 was only 65ŷ3% (n = 3) of that evoked by Ins(1,4,5)P3. Furthermore, Ins(2,4,5)P3 inhibited the peak rate of 45Ca2+ efflux evoked by Ins(1,4,5)P3. These results indicate that Ins(2,4,5)P3 is a partial agonist at hepatic Ins(1,4,5)P3 receptors. Additionally, responses to Ins(2,4,5)P3 were less positively cooperative [Hill coefficient (h) = 1.9ŷ0.3] than were those to Ins(1,4,5)P3 (h = 3.0ŷ0.2) and the kinetics of termination of 45Ca2+ mobilization were slower. The lesser efficacy of Ins(2,4,5)P3 may account for the lower cooperativity in the responses it evokes, the slower inactivation of InsP3 receptors and the characteristic patterns of Ca2+ spiking it evokes in intact cells.
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February 1997
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Research Article|
February 01 1997
Rapid kinetic measurements of 45Ca2+ mobilization reveal that Ins(2,4,5)P3 is a partial agonist at hepatic InsP3 receptors
Jonathan S. MARCHANT;
Jonathan S. MARCHANT
*Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Young-Tae CHANG;
Young-Tae CHANG
†Department of Chemistry, Pohang University of Science and Technology, San 31 Hyoja Dong, Pohang, 790-784 Korea
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Sung-Kee CHUNG;
Sung-Kee CHUNG
†Department of Chemistry, Pohang University of Science and Technology, San 31 Hyoja Dong, Pohang, 790-784 Korea
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Robin F. IRVINE;
Robin F. IRVINE
*Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Colin W. TAYLOR
Colin W. TAYLOR
‡
*Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
‡To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
October 15 1996
Revision Received:
November 28 1996
Accepted:
December 03 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 321 (3): 573–576.
Article history
Received:
October 15 1996
Revision Received:
November 28 1996
Accepted:
December 03 1996
Citation
Jonathan S. MARCHANT, Young-Tae CHANG, Sung-Kee CHUNG, Robin F. IRVINE, Colin W. TAYLOR; Rapid kinetic measurements of 45Ca2+ mobilization reveal that Ins(2,4,5)P3 is a partial agonist at hepatic InsP3 receptors. Biochem J 1 February 1997; 321 (3): 573–576. doi: https://doi.org/10.1042/bj3210573
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