Tojo K, Sato S, Tokudome G, Ohta M, Kawaguchi Y, Sakai O, Nakagawa O, Nakao K
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Biochem Biophys Res Commun. 1996 Aug 14;225(2):340-6. doi: 10.1006/bbrc.1996.1177.
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.
利用培养的新生大鼠心肌细胞，研究了促肾上腺皮质激素释放因子（CRF）在调节心房钠尿肽（ANP）和脑钠尿肽（BNP）释放中的新功能作用。用CRF（10^-10 - 10^-6 M）处理导致ANP和BNP分泌呈剂量和时间依赖性增加，分别比对照值高出2.5倍和1.8倍。该效应在6小时时显著，并持续至少36小时。CRF（10^-7 M）的作用被特异性CRF受体拮抗剂α-螺旋CRF（9-41）（10^-7 M）部分阻断。CRF（10^-7 M）的作用不仅被环磷酸腺苷依赖性蛋白激酶A（PKA）抑制剂H-89（10^-5 M）减弱，还被蛋白激酶C抑制剂H-7（50 μM）和钙泊三醇C（10^-6 M）减弱。单独使用H-7（50 μM）和钙泊三醇C（10^-6 M）可降低基础ANP和BNP水平。此外，CRF（10^-7 M）刺激蛋白质合成增加至1.2倍。这些结果表明，CRF通过CRF受体刺激ANP和BNP分泌，并且至少部分地通过心脏肥大期间的PKA激活来实现。
