Suppression of neuropeptide Y1 receptor function in SK-N-MC cells by nitric oxide.
The neuropeptide Y1 receptor (NPY1) predominantly mediates the vasoconstrictor effects of NPY in smooth muscle cells. The present experiments were planned to study the direct influence of the vasodilator nitric oxide (NO) on NPY1-receptor function. SK-N-MC and CHP-234 cells expressing Y1 and Y2 receptor, respectively, were incubated with the NO donors sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP). Receptor binding, Y1-receptor mRNA expression by Northern blot, and adenosine 3',5'-cyclic monophosphate (cAMP) and intracellular Ca2+ concentration ([Ca2+]i) responses were studied. SNP, SIN-1, and SNAP decreased normal binding of NPY to the NPY1 receptor in SK-N-MC cells in a concentration-dependent manner. SNP (500 microM), SIN-1 (1,000 microM), and SNAP (500 microM) significantly decreased binding to approximately 50%. The cell viability was not reduced. None of the NO donors affected Y2 receptor binding. Pretreatment with SNP significantly attenuated NPY-induced inhibition of cAMP formation in SK-N-MC cells but had no effect on CHP cells. The NPY-induced [Ca2+]i response was reduced to 50% by SNP pretreatment. NPY1 mRNA expression was reduced to one-third after SNAP treatment of SK-N-MC cells. In vitro, NPY1 receptor function of SK-N-MC cells is inhibited by NO-donor incubation on an mRNA level.
Dötsch
J
J
Department of Pediatrics, Justus-Liebig-Universität, Giessen, Germany.
Hänze
J
J
Beste
O
O
Behrendt
J
J
Weber
W M
WM
Dittrich
K
K
Rascher
W
W
D015152:Blotting, Northern; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000235:genetics; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D000242:Cyclic AMP; D010396:Penicillamine