Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes

Haruhiro Higashida, Alla Egorova, Chiharu Higashida, Zhen Guo Zhong, Shigeru Yokoyama, Mami Noda, Jia Sheng Zhang

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Abstract

We examined the role of cyclic ADP-ribose (cADP-ribose) as a second messenger downstream of adrenergic receptors in the heart after excitation of sympathetic neurons. To address this question, ADP-ribosyl cyclase activity was measured as the rate of [3H]cADP-ribose formation from [3H]NAD+ in a crude membrane fraction of rat ventricular myocytes. Isoproterenol at 1 μM increased ADP-ribosyl cyclase activity by 1.7-fold in ventricular muscle; this increase was inhibited by propranolol. The stimulatory effect on the cyclase was mimicked by 10 nM GTP and 10 μM guanosine 5'-3-O- (thio)triphosphate, whereas 10 μM GTP inhibited the cyclase. Cholera toxin blocked the activation of the cyclase by isoproterenol and GTP. The above effects of isoproterenol and GTP in ventricular membranes were confirmed by cyclic GDP-ribose formation fluorometrically. These results demonstrate the existence of a signal pathway from β-adrenergic receptors to membrane-bound ADP-ribosyl cyclase via G protein in the ventricular muscle cells and suggest that increased cADP-ribose synthesis is involved in up-regulation of cardiac function by sympathetic stimulation.

Original languageEnglish
Pages (from-to)33348-33354
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number47
DOIs
Publication statusPublished - Nov 19 1999

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Higashida, H., Egorova, A., Higashida, C., Zhong, Z. G., Yokoyama, S., Noda, M., & Zhang, J. S. (1999). Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes. Journal of Biological Chemistry, 274(47), 33348-33354. https://doi.org/10.1074/jbc.274.47.33348