PT  - JOURNAL ARTICLE
AU  - Susanne Keffel
AU  - Martina Schmidt
AU  - Angela Bischoff
AU  - Martin C. Michel
TI  - Neuropeptide-Y Stimulation of Extracellular Signal-Regulated Kinases in Human Erythroleukemia Cells
DP  - 1999 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1172--1178
VI  - 291
IP  - 3
4099  - http://jpet.aspetjournals.org/content/291/3/1172.short
4100  - http://jpet.aspetjournals.org/content/291/3/1172.full
SO  - J Pharmacol Exp Ther1999 Dec 01; 291
AB  - We have used human erythroleukemia (HEL) cells to investigate distal signaling mechanisms of neuropeptide-Y (NPY) receptors. NPY did not activate phospholipase D, determined as a phosphatidylethanol formation, or protein kinase C (PKC) determined enzymatically as a translocation to the plasma membrane. However, NPY caused a rapid (already maximal after 30 s) and concentration-dependent (maximum at 10–100 nM) activation of extracellular signal-regulated kinase (ERK) as assessed by immunoblotting with epitope-specific, antiphosphotyrosine antibodies and in some cases enzymatically. ERK activation by 100 nM NPY was abolished by the Y1 NPY receptor antagonist BIBP 3226 (1 μM), pertussis toxin treatment (100 ng ml−1 overnight), the mitogen-activated protein kinase (MAPK) kinase inhibitor PD 98059 (100 μM), and the phosphatidylinositol-3-kinase inhibitor wortmannin (100 nM). Whereas the PKC inhibitor staurosporine (3 μM) inhibited ERK activation by NPY, the chemically distinct PKC inhibitors calphostin C (3 μM), Gö 6976 (3 μM), and bisindolylmaleimide I (3 μM) did not. NPY did not activate other MAPK such as jun N-terminal kinase or p38 MAPK. We conclude that NPY does not activate phospholipase D, PKC, jun N-terminal kinase, or p38 MAPK in HEL cells. However, NPY activates ERK by a pathway involving Y1 receptors, pertussis toxin-sensitive G proteins, and phosphatidylinositol-3-kinase, whereas PKC may not be involved. Staurosporine may have PKC-independent effects on ERK activation. The American Society for Pharmacology and Experimental Therapeutics