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 messenge r downstream of angiotensin ii (Ang II) receptor activation in the heart? A DP-ribosyl cyclase activity was measured in a crude membrane fraction of ve ntricular myocytes. Ang II at 10-100 nM increased ADP-ribosyl cyclase activ ity by 40-90 % in the ventricular muscle of neonatal (2-4-day-old) rats, bu t not in fetal or adult hearts. This increase was inhibited by the Ang II a ntipeptide. Stimulation of ADP-ribosyl cyclase was reproduced by GTP and gu anosine 5'-[gamma -thio]triphosphate, and prevented by guanosine 5'-[beta - thio]diphosphate. Prior treatment of the rats with cholera toxin A and B su bunits also blocked the Ang II-induced activation. The density of Ang II re ceptors detected as [H-3]Ang II binding was higher in neonatal than adult r ats. These results demonstrate the existence of a signalling pathway from A ng II receptors to membrane-bound ADP-ribosyl cyclase in the ventricular mu scle cell and suggest that the Ang II-induced increase in cADP-ribose synth esis is involved in the regulation of cardiac function and development.