Hypertrophic growth of cultured neonatal rat heart cells mediated by vasopressin V(1A) receptor.
Primary cultures of neonatal cardiac myocytes were used to determine both the identity of second messengers that are involved in vasopressin receptor-mediated effects on cardiac hypertrophy and the type of vasopressin receptor that is involved in vasopressin-induced cell growth. Neonatal rat myocytes were plated at a density of 1x10(6) cells per 60 mm dish and were incubated with serum-free medium for 7 days. Treatment of myocytes with vasopressin significantly increased the RNA-to-DNA ratio, by 18-25%, at culture days 4-6 and the protein-to-DNA ratio by 18-20% at culture days 5-7. Rates of protein synthesis were determined to assess their contribution to protein contents during myocyte growth. Vasopressin significantly accelerated rates of protein synthesis by 25% at culture day 6. Intracellular free Ca(2+) ([Ca(2+)](i)) was transiently increased after vasopressin exposure. After the peak increase in [Ca(2+)](i) at less than 30 s, there was a sustained increase for at least 5 min. The specific activity of protein kinase C in the particulate fraction was increased rapidly after exposure to vasopressin, and its activity remained higher for 30 min, returning to its control level within 60 min. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to vasopressin. After vasopressin treatment, the content of c-fos mRNA was increased. The stimulatory effects of vasopressin on these parameters were significantly inhibited by vasopressin V(1A) receptor antagonist, OPC-21268, but not by vasopressin V(2) receptor antagonist, OPC-31260. These results suggest that vasopressin directly induces myocyte hypertrophic growth via the V(1A) receptor in neonatal rat heart cells.
Nakamura
Y
Y
First Department of Internal Medicine, Asahikawa Medical College, Nishikagura 4-5, Asahikawa, Hokkaido, Japan.
Haneda
T
T
Osaki
J
J
Miyata
S
S
Kikuchi
K
K
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010880:Piperidines / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D003470:Culture Media; D010880:Piperidines; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D015363:Quinolones; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D014667:Vasopressins; C068644:OPC 21268; C076251:mozavaptan; D004247:DNA; D011493:Protein Kinase C; D002118:Calcium