Stimulation by corticotropin-releasing factor of atrial natriuretic peptide and brain natriuretic peptide secretions from cultured neonatal rat cardiomyocytes.
The new functional role of corticotropin-releasing factor (CRF) in the regulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) release was investigated using cultured neonatal rat cardiomyocytes. Treatment with CRF (10(-10)-10(-6) M) resulted in dose- and time-dependent increase in ANP and BNP secretion, up to 2.5-fold and 1.8-fold above control values, respectively. The effect was significant at 6 hr and persisted for at least 36 hr. The effect of CRF (10(-7) M) was partially blocked by alpha-helical CRF(9-41) (10(-7) M), a specific CRF receptor antagonist. The effect of CRF (10(-7) M) was not only blunted by cAMP-dependent protein kinase A (PKA) inhibitor, H-89 (10(-5) M), but also by protein kinase C inhibitors, H-7 (50 microM) and Calphostin C (10(-6) M). H-7 (50 microM) and Calphostin C (10(-6) M) alone lowered basal ANP and BNP levels. Furthermore, CRF (10(-7) M) stimulates protein synthesis up to 1.2-fold. These results indicate that CRF stimulates ANP and BNP secretions through the CRF receptor and, at least in part, via PKA activation during cardiac hypertrophy.
Tojo
K
K
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Sato
S
S
Tokudome
G
G
Ohta
M
M
Kawaguchi
Y
Y
Sakai
O
O
Nakagawa
O
O
Nakao
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides; D014316:Tritium
D007546:Isoquinolines; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014316:Tritium; D020097:Natriuretic Peptide, Brain; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone; D007930:Leucine; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide