Angiotensin II stimulates cyclic ADP-ribose formation in neonatal rat cardiac myocytes

• Published in: Biochemical journal Vol. 352 Pt 1; no. 1; pp. 197 - 202
• Main Authors: Higashida, H, Zhang, J, Hashii, M, Shintaku, M, Higashida, C, Takeda, Y
• Format: Journal Article
• Language: English
• Published: England 15-11-2000
• Subjects: Adenosine Diphosphate Ribose - analogs & derivatives; Adenosine Diphosphate Ribose - metabolism; Age Factors; Angiotensin II - metabolism; Animals; Animals, Newborn; Cell Membrane - enzymology; Cells, Cultured; Cholera Toxin - pharmacology; Chromatography, Thin Layer; Cyclic ADP-Ribose; Dose-Response Relationship, Drug; Fluorometry; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Guanosine Diphosphate - analogs & derivatives; Guanosine Diphosphate - pharmacology; Guanosine Triphosphate - metabolism; Guanosine Triphosphate - pharmacology; Heart - embryology; Myocardium - cytology; Myocardium - enzymology; Protein Binding; Rats; Rats, Wistar; Signal Transduction; Thionucleotides - pharmacology; Time Factors
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/0264-6021:3520197

To examine the role of cyclic ADP-ribose (cADP-ribose) as a second messenger downstream of angiotensin II (Ang II) receptor activation in the heart, ADP-ribosyl cyclase activity was measured in a crude membrane fraction of ventricular myocytes. Ang II at 10-100 nM increased ADP-ribosyl cyclase activity by 40-90% in the ventricular muscle of neonatal (2-4-day-old) rats, but not in fetal or adult hearts. This increase was inhibited by the Ang II antipeptide. Stimulation of ADP-ribosyl cyclase was reproduced by GTP and guanosine 5'-[gamma-thio]triphosphate, and prevented by guanosine 5'-[beta-thio]diphosphate. Prior treatment of the rats with cholera toxin A and B subunits also blocked the Ang II-induced activation. The density of Ang II receptors detected as [(3)H]Ang II binding was higher in neonatal than adult rats. These results demonstrate the existence of a signalling pathway from Ang II receptors to membrane-bound ADP-ribosyl cyclase in the ventricular muscle cell and suggest that the Ang II-induced increase in cADP-ribose synthesis is involved in the regulation of cardiac function and development.