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

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Désaubry, L. Articles by Johnson, R. A. Search for Related Content PubMed PubMed Citation Articles by Désaubry, L. Articles by Johnson, R. A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 38, 24972-24977, September 18, 1998

Adenine Nucleoside 3'-Tetraphosphates Are Novel and Potent Inhibitors of Adenylyl Cyclases

From the Department of Physiology and Biophysics, State University of New York, Health Sciences Center, Stony Brook, New York 11794-8661

2'-Deoxyadenosine 3'-tetraphosphate (2'-deoxy-3'-A₄P) and 2',5'-dideoxyadenosine 3'-tetraphosphate (2',5'-dideoxy-3'-A₄P) were synthesized, and their effects were tested on crude and purified forms of native adenylyl cyclases isolated from brain. Syntheses combined the method of alkoxide activation with the use of tribromoethyl phosphoromorpholino-chloridate as an initial phosphorylating agent. Inhibition of adenylyl cyclase was rapid in onset. With 2'-d-3'-A₄P or 2',5'-dd-3'-A₄P inhibition of a purified native enzyme conformed to a linear noncompetitive behavior with respect to substrate, metal-5'ATP. Order of potency was 2',5'-dideoxy- > 2'-deoxyadenosine and 3'-tetraphosphate > 3'-triphosphate. Both mechanism of inhibition and rank order of potency were consistent with inhibition via the 3'-nucleotide-(P)-site on adenylyl cyclase. Neither 2',5'-dd-3'-ATP nor 2',5'-dd-3'-A₄P had any effect on the activities of other adenosine nucleotide binding proteins such as Ca²⁺/calmodulin-sensitive cyclic nucleotide phosphodiesterase, Na⁺/K⁺-ATPase, or cAMP-dependent protein kinase. With purified adenylyl cyclase from bovine brain 2',5'-dd-3'-A₄P and 2'-d-3'-A₄P gave, respectively, IC₅₀ values of 9.3 and 15 nM and K_i values of 23 and 53 nM. These 3'-nucleotides are the most potent regulators described for adenylyl cyclases.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. Chernogubova, D. S. Hutchinson, J. Nedergaard, and T. Bengtsson {alpha}1- and {beta}1-Adrenoceptor Signaling Fully Compensates for {beta}3-Adrenoceptor Deficiency in Brown Adipocyte Norepinephrine-Stimulated Glucose Uptake Endocrinology, May 1, 2005; 146(5): 2271 - 2284. [Abstract] [Full Text] [PDF]

				A. Gille, G. H. Lushington, T.-C. Mou, M. B. Doughty, R. A. Johnson, and R. Seifert Differential Inhibition of Adenylyl Cyclase Isoforms and Soluble Guanylyl Cyclase by Purine and Pyrimidine Nucleotides J. Biol. Chem., May 7, 2004; 279(19): 19955 - 19969. [Abstract] [Full Text] [PDF]

				W. H. G. Laux, P. Pande, I. Shoshani, J. Gao, V. Boudou-Vivet, G. Gosselin, and R. A. Johnson Pro-nucleotide Inhibitors of Adenylyl Cyclases in Intact Cells J. Biol. Chem., April 2, 2004; 279(14): 13317 - 13332. [Abstract] [Full Text] [PDF]

				E. Chernogubova, B. Cannon, and T. Bengtsson Norepinephrine Increases Glucose Transport in Brown Adipocytes via {beta}3-Adrenoceptors through a cAMP, PKA, and PI3-Kinase-Dependent Pathway Stimulating Conventional and Novel PKCs Endocrinology, January 1, 2004; 145(1): 269 - 280. [Abstract] [Full Text] [PDF]

				A. Gille and R. Seifert 2'(3')-O-(N-Methylanthraniloyl)-substituted GTP Analogs: A Novel Class of Potent Competitive Adenylyl Cyclase Inhibitors J. Biol. Chem., April 4, 2003; 278(15): 12672 - 12679. [Abstract] [Full Text] [PDF]

				N. Defer, M. Best-Belpomme, and J. Hanoune Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase Am J Physiol Renal Physiol, September 1, 2000; 279(3): F400 - F416. [Abstract] [Full Text] [PDF]

				I. Shoshani, V. Boudou, C. Pierra, G. Gosselin, and R. A. Johnson Enzymatic Synthesis of Unlabeled and beta -32P-labeled beta -L-2',3'-Dideoxyadenosine-5'-triphosphate as a Potent Inhibitor of Adenylyl Cyclases and Its Use as Reversible Binding Ligand J. Biol. Chem., December 3, 1999; 274(49): 34735 - 34741. [Abstract] [Full Text] [PDF]

				I. Shoshani, W. H. G. Laux, C. Perigaud, G. Gosselin, and R. A. Johnson Inhibition of Adenylyl Cyclase by Acyclic Nucleoside Phosphonate Antiviral Agents J. Biol. Chem., December 3, 1999; 274(49): 34742 - 34744. [Abstract] [Full Text] [PDF]

				J. H. Hurley Structure, Mechanism, and Regulation of Mammalian Adenylyl Cyclase J. Biol. Chem., March 19, 1999; 274(12): 7599 - 7602. [Full Text] [PDF]

				A. Ibrahimi, N. Abumrad, H. Maghareie, M. Golia, I. Shoshani, L. Desaubry, and R. A. Johnson Adenylyl cyclase P-site ligands accelerate differentiation in Ob1771 preadipocytes Am J Physiol Cell Physiol, February 1, 1999; 276(2): C487 - C496. [Abstract] [Full Text] [PDF]

				S. Doronin, C. Dessauer, and R. A. Johnson Direct Photoaffinity Labeling of Individual Cytosolic Domains of Adenylyl Cyclase by [32P]2'-deoxy-3'-AMP and [alpha -32P]5'-ATP J. Biol. Chem., December 4, 1998; 273(49): 32416 - 32420. [Abstract] [Full Text] [PDF]