scholarly journals Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and its analogs as stable mimics of Ca2+-mobilizing second messenger cyclic ADP-ribose

2001 ◽  
Vol 1 (1) ◽  
pp. 5-6
Author(s):  
S. Shuto ◽  
T. Kudoh ◽  
M. Fukuoka ◽  
Y. Ueno ◽  
A. Matsuda
2005 ◽  
Vol 280 (16) ◽  
pp. 15952-15959 ◽  
Author(s):  
Andreas H. Guse ◽  
Xianfeng Gu ◽  
Liangren Zhang ◽  
Karin Weber ◽  
Elisabeth Krämer ◽  
...  

Cyclic ADP-ribose (cADPR) is an endogenous Ca2+-mobilizing second messenger in many cell types and organisms. Although the biological activity of several modified analogues of cADPR has been analyzed, most of these structures were still very similar to the original molecule. Recently, we have introduced simplified analogues in which the northern ribose (N1-linked ribose) was replaced by an ether strand (Gu, X., Yang, Z., Zhang, L., Kunerth, S., Fliegert, R., Weber, K., Guse, A. H., and Zhang, L. (2004)J. Med. Chem.47, 5674–5682). Here we also demonstrate that the southern ribose (N9-linked ribose) can be replaced by an ether strand resulting inN1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthinecyclic pyrophosphate (cIDP-DE). This minimal structural analogue of cyclic ADP-ribose released Ca2+from intracellular stores of permeabilized Jurkat T lymphocytes. In intact T lymphocytes initial subcellular Ca2+release events, global Ca2+release, and subsequent global Ca2+entry were observed. Cardiac myocytes freshly prepared from mice responded to cIDP-DE by increased recruitment of localized Ca2+signals and by global Ca2+waves.


1998 ◽  
Vol 274 (6) ◽  
pp. C1653-C1660 ◽  
Author(s):  
Y. S. Prakash ◽  
Mathur S. Kannan ◽  
Timothy F. Walseth ◽  
Gary C. Sieck

The purpose of the present study was to determine whether cyclic ADP-ribose (cADPR) acts as a second messenger for Ca2+ release through ryanodine receptor (RyR) channels in tracheal smooth muscle (TSM). Freshly dissociated porcine TSM cells were permeabilized with β-escin, and real-time confocal microscopy was used to examine changes in intracellular Ca2+ concentration ([Ca2+]i). cADPR (10 nM–10 μM) induced a dose-dependent increase in [Ca2+]i, which was blocked by the cADPR receptor antagonist 8-amino-cADPR (20 μM) and by the RyR blockers ruthenium red (10 μM) and ryanodine (10 μM), but not by the inositol 1,4,5-trisphosphate receptor blocker heparin (0.5 mg/ml). During steady-state [Ca2+]ioscillations induced by acetylcholine (ACh), addition of 100 nM and 1 μM cADPR increased oscillation frequency and decreased peak-to-trough amplitude. ACh-induced [Ca2+]ioscillations were blocked by 8-amino-cADPR; however, 8-amino-cADPR did not block the [Ca2+]iresponse to a subsequent exposure to caffeine. These results indicate that cADPR acts as a second messenger for Ca2+ release through RyR channels in TSM cells and may be necessary for initiating ACh-induced [Ca2+]ioscillations.


1991 ◽  
Vol 69 (2) ◽  
pp. 181-184 ◽  
Author(s):  
J. Kraicer ◽  
M. B. French ◽  
B. T. Lussier ◽  
B. C. Moor ◽  
P. Brazeau

The purpose of this study was to characterize the biological activity of the synthetic rat growth hormone releasing factor analogue rGRF(1–29)NH2 and to compare its action on growth hormone (GH) release to that of authentic rGRF(1–43)OH. We first compared the concentration–response characteristics of the two peptides in static incubation, and then examined the reversibility and repeatability of the GH response in a perifusion system. Authentic rGRF(1–43)OH was significantly more potent in static incubation (EC50 = 3 × 10−11 M) than the analogue (5 × 10−11 M), whereas the reverse held true in perifusion. The shapes of the GH responses were similar for both peptides in the perifusion system. However, while the GH response to authentic rGRF was repeatable, the prior administration of rGRF(1–29)NH2 significantly reduced (>50%) the GH response to the subsequent administration of either rGRF(1–29)NH2 or rGRF(1–43)OH. Thus authentic rGRF and the synthetic fragment may have different actions at the level of the GRF receptor or at a postreceptor (second messenger) step.Key words: growth hormone, growth hormone releasing factor, adenohypophysis.


2008 ◽  
Vol 283 (47) ◽  
pp. 32188-32197 ◽  
Author(s):  
Santina Bruzzone ◽  
Nicoletta Bodrato ◽  
Cesare Usai ◽  
Lucrezia Guida ◽  
Iliana Moreschi ◽  
...  

2001 ◽  
Vol 76 (2) ◽  
pp. 321-331 ◽  
Author(s):  
Haruhiro Higashida ◽  
Minako Hashii ◽  
Shigeru Yokoyama ◽  
Naoto Hoshi ◽  
Kiyofumi Asai ◽  
...  

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