Kimura M, Ogihara M
Biochemical Pharmacology Group, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Biol Pharm Bull. 1998 Jan;21(1):22-8. doi: 10.1248/bpb.21.22.
We investigated the effects of hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) on the expression of alpha2- and beta2-adrenergic responses in primary cultures of adult rat hepatocytes. HGF (1 and 5 ng/ml) rapidly stimulated the expression of beta2-adrenergic responses and significantly increased alpha2-adrenergic responses with a maximal response at 21 h. The stimulatory effects of HGF were reduced dependent on the initial plating density and were completely blocked by cycloheximide (5 microM). On the other hand, PDGF (10 ng/ml) significantly increased the beta2-adrenergic response, but only slightly increased the alpha2-adrenergic responses. Expression of the alpha2- and beta2-adrenergic responses by PDGF was independent of the initial plating density. The expression of these responses was blocked by cycloheximide (5 microM). Northern blot analysis of the hepatocyte mRNA showed increased expression induced by the HGF and PDGF of the both alpha2- and beta2-adrenergic receptor mRNA, and this expression was inhibited by actinomycin D (5 ng/ml). These results indicate that the expression of alpha2- and beta2-adrenergic responses produced by these two growth factors is regulated differently by the cell density of the primary cultures. The results suggest that the expression of alpha2- and beta2-adrenergic responses is mediated through increased synthesis of these receptor proteins.
我们研究了肝细胞生长因子(HGF)和血小板衍生生长因子(PDGF)对成年大鼠原代肝细胞中α2-和β2-肾上腺素能反应表达的影响。HGF(1和5 ng/ml)迅速刺激β2-肾上腺素能反应的表达,并显著增加α2-肾上腺素能反应,在21小时时达到最大反应。HGF的刺激作用根据初始接种密度而降低,并被放线菌酮(5 microM)完全阻断。另一方面,PDGF(10 ng/ml)显著增加β2-肾上腺素能反应,但仅轻微增加α2-肾上腺素能反应。PDGF诱导的α2-和β2-肾上腺素能反应的表达与初始接种密度无关。这些反应的表达被放线菌酮(5 microM)阻断。对肝细胞mRNA的Northern印迹分析显示,HGF和PDGF均诱导α2-和β2-肾上腺素能受体mRNA表达增加,且这种表达被放线菌素D(5 ng/ml)抑制。这些结果表明,这两种生长因子产生的α2-和β2-肾上腺素能反应的表达受原代培养细胞密度的不同调节。结果表明,α2-和β2-肾上腺素能反应的表达是通过这些受体蛋白合成增加介导的。