Angiotensin II stimulates cyclic ADP-ribose formation in neonatal rat cardiac myocytes.
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.
Higashida
H
H
Department of Biochemical Genetics, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan. haruhiro@med.kanazawa-u.ac.jp
Zhang
J
J
Hashii
M
M
Shintaku
M
M
Higashida
C
C
Takeda
Y
Y
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism*; D000367:Age Factors; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D036563:Cyclic ADP-Ribose; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000196:embryology; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D013873:Thionucleotides; D000804:Angiotensin II; D036563:Cyclic ADP-Ribose; D006153:Guanosine Diphosphate; D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D006160:Guanosine Triphosphate; D002772:Cholera Toxin