Back to Search
Start Over
Turnover of bis-diphosphoinositol tetrakisphosphate in a smooth muscle cell line is regulated by ß2-adrenergic receptors through a cAMP-mediated, A-kinase-independent mechanism.
- Source :
-
EMBO Journal . 3/15/98, Vol. 17 Issue 6, p1710-1716. 7p. - Publication Year :
- 1998
-
Abstract
- Bis­diphosphoinositol tetrakisphosphate ([PP]2-InsP4 or ‘InsP8’) is a ‘high-energy’ inositol phosphate; we report that its metabolism is receptor-regulated in DDT1 MF-2 smooth muscle cells. This conclusion arose by pursuing the mechanism by which F­ decreased cellular levels of [PP]2-InsP4 up to 70%. A similar effect was induced by elevating cyclic nucleotide levels, either with IBMX or by application of either Bt2cAMP (EC50 = 14.7 μM), Bt2cGMP (EC50 = 7.9 μM) or isoproterenol (EC50 = 0.4 nM). Isoproterenol (1 μM) decreased [PP]2-InsP4 levels 25% by 5 min, and 71% by 60 min. This novel, agonist-mediated regulation of [PP]2-InsP4 turnover was very specific; isoproterenol did not decrease the cellular levels of either inositol pentakisphosphate, inositol hexakisphosphate or other diphosphorylated inositol polyphosphates. Bradykinin, which activated phospholipase C, did not affect [PP]2-InsP4 levels. Regulation of [PP]2-InsP4 turnover by both isoproterenol and cell-permeant cyclic nucleotides was unaffected by inhibitors of protein kinases A and G. The effectiveness of the kinase inhibitors was confirmed by their ability to block phosphorylation of the cAMP response element-binding protein. Our results indicate a new signaling action of cAMP, and furnish an important focus for future research into the roles of diphosphorylated inositol phosphates in signal transduction. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 17
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 13006109
- Full Text :
- https://doi.org/10.1093/emboj/17.6.1710