Synonym, Antonym oder etwas dazwischen?

Klimaanpassung ist eine komplexe Herausforderung für die Gesellschaft und ihre Akteure. Mit Nach haltigkeit soll „(…) etwas bewahrt werden zum Wohl der zukünftigen Generationen“, so Bernd Klauer. Gleiches gilt für die Anpassung an den Klimawandel und trotz dieser ähnlichen Ziele wird bisher in diesem Rahmen zu wenig auf Nachhaltigkeit geachtet

Tyr-c[D-Orn-Tyr(Bzl)-Pro-Gly]: a novel antiproliferative acting somatostatin receptor agonist with μ-opioid receptor-sensitizing properties

1. Here, we introduce a β-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[D-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. 2. This opioid-derived peptide possesses only low affinity for μ-receptors, but enhances the agonist binding to μ-receptors in vitro and potentiates the analgesic effect of morphin in vivo. The molecular mechanism of μ-receptor sensitization by cCD-2 is not yet known. 3. The antiproliferative effect of cCD-2 is independent of μ-, δ-, and κ-receptors. 4. Using SH-SY5Y cells as model, we can demonstrate that cCD-2 specifically binds to somatostatin receptors and stimulates the activity of protein tyrosine phosphatases, which are early downstream targets of SST receptors. 5. In SH-SY5Y cells, cCD-2 specifically increases the activity of the cytosolic PTP SHP-2, stimulates the activity of mitogen-activated protein kinase (MAPK), and elevates the expression of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1), suggesting the involvement of SSTR1 receptor subtype in cCD-2 action in this cell type. 6. In COS-7 cells, for comparison, we found a stimulation of SHP-2 as well as SHP-1 in response to cCD-2. The activation of SHP-1, which is attributed to the SSTR2 receptor and negatively regulates the EGF receptor, corresponds with the ability of cCD-2 to inhibit the EGF-induced MAPK activation in COS-7 cells. 7. Our results show that in SH-SY5Y cells cCD-2 inhibits cell growth via the SSTR1 receptor-signalling pathway but may, in other cells, also use other SSTR subtypes and their signalling mechanisms. 8. cCD-2 represents a novel type of opioid-derived antiproliferative SST receptor agonist, which possesses low μ-receptor affinity but may induce μ-receptor sensitization and is structurally different from the hitherto known SST receptor agonists