Modulation of the beta-adrenergic-response in cultured rat heart cells

✍ Scribed by Gerd Wallukat; Frank-D. Boehmer; Ulla Engstroem; Peter Langen; Morley Hollenberg; Joachim Behlke; Hartmut Kuehn; Richard Grosse

• Publisher: Springer
• Year: 1991
• Tongue: English
• Weight: 806 KB
• Volume: 102
• Category: Article
• ISSN: 0300-8177
• DOI: 10.1007/bf00232157

✦ Synopsis

'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.