Downregulation of adenylylcyclase types V and VI mRNA levels in pacing-induced heart failure in dogs.
We have shown that the heart expresses two distinct forms of adenylylcyclase mRNA, types V and VI. In this study we have characterized the expression of these two mRNA species in heart failure generated by overdrive pacing at a rate of 240 beats/min. After 4 wk, left ventricular end-diastolic pressure and heart rate increased significantly with the appearance of signs of heart failure, i.e., edema, ascites, and exercise intolerance. Basal as well as forskolin-stimulated adenylylcyclase activities decreased significantly, which was accompanied by a reduction in the steady state mRNA levels of adenylylcyclase types V and VI. These data suggest that in this model of cardiomyopathy, the downregulation of adenylylcyclase catalytic activity results, at least in part, from a reduction in the steady state levels of types V and VI adenylylcyclase mRNA levels.
Ishikawa
Y
Y
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York 10032.
Sorota
S
S
Kiuchi
K
K
Shannon
R P
RP
Komamura
K
K
Katsushika
S
S
Vatner
D E
DE
Vatner
S F
SF
Homcy
C J
CJ
D000262:Adenylyl Cyclases / Q000235:genetics*; D000818:Animals; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D006333:Heart Failure / Q000201:enzymology*; D006339:Heart Rate; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D014018:Tissue Distribution
D007527:Isoenzymes; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases