AJP - Cell Physiology, Vol 273, Issue 2 C618-C621, Copyright © 1997 by American Physiological Society
Suppression of neuropeptide Y1 receptor function in SK-N-MC cells by nitric oxide
J. Dotsch, J. Hanze, O. Beste, J. Behrendt, W. M. Weber, K. Dittrich and W. Rascher
Department of Pediatrics, Justus-Liebig-Universitat, Giessen, Germany.
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.
