Wallukat G, Boehmer F D, Engstroem U, Langen P, Hollenberg M, Behlke J, Kuehn H, Grosse R
Central Institute for Cardiovascular Research, Academy of Sciences, Berlin-Buch, Germany.
Mol Cell Biochem. 1991 Mar 27;102(1):49-60. doi: 10.1007/BF00232157.
'Mammary-derived growth inhibitor (MDGI)' is a 14.5 kDa polypeptide with growth-inhibitory activity for various mammary epithelial cells in vitro which is highly homologous to cardiac fatty acid-binding protein (H-FABP). Here we describe a new biological activity of MDGI: Inhibition of L(+)-lactate-, arachidonic acid- and 15-S-hydroxyeicosatetraenoic acid-induced supersensitivity of neonatal rat heart cells for beta-adrenergic stimulation, concerning particularly a small population of beta 2-receptors. Synthetic peptides corresponding to the MDGI-sequence, residue 121-131 mimic the effect of MDGI. Measurements of lipid-binding to MDGI and synthetic peptides excluded the binding of arachidonic acid, 15-S-hydroxyeicosatetraenoic acid or beta-adrenergic agonists to MDGI or the peptides as the mechanism for this effect. Also, no direct interference of MDGI and the synthetic peptides with the binding of the beta-adrenergic agent CGP 12177 to its receptor on A431 cells could be detected. We suggest that MDGI and the peptides act by interference with the function of the beta 2-adrenergic receptor and that this mechanism might also be relevant for the growth-inhibitory activity of MDGI. Furthermore, the data point to a possible function of H-FABP for the modulation of beta-adrenergic sensitivity of cardiac myocytes.
“乳腺衍生生长抑制剂（MDGI）”是一种14.5 kDa的多肽，在体外对多种乳腺上皮细胞具有生长抑制活性，与心脏脂肪酸结合蛋白（H-FABP）高度同源。在此，我们描述了MDGI的一种新的生物学活性：抑制L（+）-乳酸、花生四烯酸和15-S-羟基二十碳四烯酸诱导的新生大鼠心脏细胞对β-肾上腺素能刺激的超敏感性，尤其涉及一小部分β2受体。与MDGI序列（第121-131位残基）对应的合成肽模拟了MDGI的作用。对MDGI和合成肽的脂质结合测量排除了花生四烯酸、15-S-羟基二十碳四烯酸或β-肾上腺素能激动剂与MDGI或肽结合作为这种作用机制的可能性。此外，未检测到MDGI和合成肽对β-肾上腺素能药物CGP 12177与其在A431细胞上的受体结合有直接干扰。我们认为MDGI和肽通过干扰β2肾上腺素能受体的功能起作用，并且这种机制可能也与MDGI的生长抑制活性有关。此外，数据表明H-FABP可能具有调节心肌细胞β-肾上腺素能敏感性的功能。
