![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 282, Issue 1, 475-484, 1997
Department of Pharmacology (S.G., Y.H., Y.A., M.K.) and
Central
Research Institute (J.N.), Hokkaido University School of Medicine,
Sapporo 060, Japan
The aim of this study was to explore the cellular mechanisms underlying
the impaired contractile response to beta adrenoceptor stimulation in diabetic hearts. Chronic diabetes was induced in rats by
a streptozotocin injection. Four to six weeks later, papillary muscles
isolated from diabetic hearts exhibited marked reductions in the
positive inotropic responses to isoproterenol, norepinephrine and
epinephrine. The contractile responses to forskolin,
3-isobutyl-1-methylxanthine and dibutylic cyclic AMP were also
prominently depressed. The density of beta adrenoceptors
was decreased by 50%. However, competitive binding studies with
isoproterenol showed no difference in the proportion of
beta adrenoceptors with high-affinity binding between control and diabetic myocardial membranes. Determination of the levels
of the alpha subunits of Gs and
Gi by immunoblotting revealed markedly less expression of
Gi in diabetic myocardium. The abilities of isoproterenol,
sodium fluoride, 5
-guanylyl imidodiphosphate and forskolin to
stimulate adenylate cyclase were preserved well in membranes prepared
from diabetic hearts. Nevertheless, neither stimulation of
beta adrenoceptors with isoproterenol nor direct activation of adenylate cyclase with forskolin evoked any significant increase in the degree of phosphorylation of phospholamban in diabetic
hearts. These results suggest that impaired contractile response to
beta adrenoceptor stimulation is not caused by an alteration in the beta
adrenoceptors-Gs-adenylate cyclase system, but is possibly
caused by an alteration in cellular function beyond the step of
adenylate cyclase activation.
This article has been cited by other articles:
|
|
 |
|
  J. Amour, X. Loyer, P. Michelet, A. Birenbaum, B. Riou, and C. Heymes Preservation of the Positive Lusitropic Effect of {beta}-Adrenoceptors Stimulation in Diabetic Cardiomyopathy Anesth. Analg., October 1, 2008; 107(4): 1130 - 1138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Bidasee, H. Zheng, C.-H. Shao, S. K. Parbhu, G. J. Rozanski, and K. P. Patel Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of {beta}-adrenoceptors J Appl Physiol, September 1, 2008; 105(3): 907 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Yang, V. R. Tuniki, S. Anjaiah, J. R. Falck, C. J. Hillard, and W. B. Campbell Characterization of Epoxyeicosatrienoic Acid Binding Site in U937 Membranes Using a Novel Radiolabeled Agonist, 20-125I-14,15-Epoxyeicosa-8(Z)-Enoic Acid J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1019 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Aragno, R. Mastrocola, G. Alloatti, I. Vercellinatto, P. Bardini, S. Geuna, M. G. Catalano, O. Danni, and G. Boccuzzi Oxidative Stress Triggers Cardiac Fibrosis in the Heart of Diabetic Rats Endocrinology, January 1, 2008; 149(1): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ito, Y. Hayashi, Y. Kawai, M. Iwasaki, K. Takada, T. Kamibayashi, A. Yamatodani, and T. Mashimo Diabetes mellitus reduces the antiarrhythmic effect of ion channel blockers. Anesth. Analg., September 1, 2006; 103(3): 545 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Malhotra, R. Begley, B. P. S. Kang, I. Rana, J. Liu, G. Yang, D. Mochly-Rosen, and L. G. Meggs PKC-{varepsilon}-dependent survival signals in diabetic hearts Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1343 - H1350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hashim, Y. Li, A. Nagakura, S. Takeo, and M. B Anand-Srivastava Modulation of G-protein expression and adenylyl cyclase signaling by high glucose in vascular smooth muscle Cardiovasc Res, September 1, 2004; 63(4): 709 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhong, P. J Reiser, and M. A. Matlib Gender differences in myosin heavy chain-{beta} and phosphorylated phospholamban in diabetic rat hearts Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2688 - H2693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishitani, Y. Hattori, F. Sakuraya, H. Onozuka, T. Makino, N. Matsuda, S. Gando, and O. Kemmotsu Effects of Ca2+ Sensitizers on Contraction, [Ca2+]i Transient and Myofilament Ca2+ Sensitivity in Diabetic Rat Myocardium: Potential Usefulness as Inotropic Agents J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 613 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. D. Dinçer, K. R. Bidasee, S. Güner, A. Tay, A. T. Özçelikay, and V. M. Altan The Effect of Diabetes on Expression of {beta}1-, {beta}2-, and {beta}3-Adrenoreceptors in Rat Hearts Diabetes, February 1, 2001; 50(2): 455 - 461. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Hattori, N. Matsuda, A. Sato, S. Watanuki, H. Tomioka, H. Kawasaki, and M. Kanno Predominant Contribution of the G Protein-Mediated Mechanism to NaF-Induced Vascular Contractions in Diabetic Rats: Association with an Increased Level of Gqalpha Expression J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 761 - 768. [Abstract] [Full Text]
|
|
|
|
|
|
A. Tamada, Y. Hattori, H. Houzen, Y. Yamada, I. Sakuma, A. Kitabatake, and M. Kanno Effects of beta -adrenoceptor stimulation on contractility, [Ca2+]i, and Ca2+ current in diabetic rat cardiomyocytes Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H1849 - H1857. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
