Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes.
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 [(3)H]cADP-ribose formation from [(3)H]NAD(+) in a crude membrane fraction of rat ventricular myocytes. Isoproterenol at 1 microM 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 microM guanosine 5'-3-O-(thio)triphosphate, whereas 10 microM 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 beta-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.
Higashida
H
H
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan. Haruhiro@med.kanazawa-u.ac.jp
Egorova
A
A
Higashida
C
C
Zhong
Z G
ZG
Yokoyama
S
S
Noda
M
M
Zhang
J S
JS
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D016466:CHO Cells; D002772:Cholera Toxin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D036563:Cyclic ADP-Ribose; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008562:Membrane Glycoproteins; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D013564:Sympathetic Nervous System / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D007545:Isoproterenol