HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirata, M. Articles by Koga, T. Search for Related Content PubMed PubMed Citation Articles by Hirata, M. Articles by Koga, T. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 264, Issue 34, 20303-20308, Dec, 1989

Synthetic inositol trisphosphate analogs and their effects on phosphatase, kinase, and the release of Ca2+

M Hirata, Y Watanabe, T Ishimatsu, T Ikebe, Y Kimura, K Yamaguchi, S Ozaki and T Koga
Department of Biochemistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.

A series of inositol 1,4,5-trisphosphate (IP3) analogs and positional isomers was examined to explore the structure-activity relationships among IP3 5-phosphatase, IP3 3-kinase, and the release of Ca2+. All analogs with additional groups on the 2nd position of IP3 inhibited the hydrolysis of [5-32P]IP3 catalyzed by erythrocyte ghosts, with a lower Ki value than seen with IP3. IP3 dehydroxylated at the 2nd position also had a lower Ki, while 2,4,5-IP3 or cyclic(1:2), 4,5-IP3 had higher Ki values. Among these compounds 2-deoxy-IP3 was as potent as IP3 in inhibiting the phosphorylation by [3H] IP3-3-kinase in rat brain cytosol. The other compounds, except for 2,4,5-IP3 inhibited the phosphorylation, however, 2-30 times higher concentrations were required. By lowering free Ca2+, the concentrations required for half- maximal inhibition were low, while those of IP3, 2-deoxy-IP3, and positional isomers remained unchanged. These compounds acted as full agonists in releasing Ca2+ from permeabilized macrophages, although 1.6- 50-fold higher concentrations than IP3 were required. These compounds also inhibited the binding of [3H]IP3 to rat cerebellum and bovine adrenal cortex microsomes, but the potencies were 2.9-33 times less than that of IP3. Thus, the 2nd position of IP3 can be modified with only a slight loss of biological activity.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Laporte, A. Hui, and I. Laher Pharmacological Modulation of Sarcoplasmic Reticulum Function in Smooth Muscle Pharmacol. Rev., December 1, 2004; 56(4): 439 - 513. [Abstract] [Full Text] [PDF]

				Q.-K. Tran, K. Ohashi, and H. Watanabe Calcium signalling in endothelial cells Cardiovasc Res, October 1, 2000; 48(1): 13 - 22. [Abstract] [Full Text] [PDF]

				C. T. Murphy, A. M. Riley, S. J. Mills, C. J. Lindley, B. V. L. Potter, and J. Westwick myo-Inositol 1,4,6-Trisphosphorothioate and myo-Inositol 1,3,6-Trisphosphorothioate: Partial Agonists with Very Low Intrinsic Activity at the Platelet myo-Inositol 1,4,5-Trisphosphate Receptor Mol. Pharmacol., March 1, 2000; 57(3): 595 - 601. [Abstract] [Full Text]