Neuropeptide Y inhibits chromaffin cell nicotinic receptor-stimulated tyrosine hydroxylase activity through a receptor-linked G protein-mediated process

Acetylcholine stimulation of bovine chromaffin cells results in increased norepinephrine and epinephrine secretion accompa-nied by a corresponding increase in synthesis. The addition of neuropeptide Y (NPY) to the culture medium prevents the in-crease in catecholamine synthesis but not secretion. Treatment of chromaffin cells with nicotine produces a concentration-dependent increase in tyrosine hydroxylase activity (IC50 5 1.2 mM) that is reduced if NPY is present during stimulation. Ty-rosine hydroxylase activity decreases in a concentration-de-pendent fashion if increasing amounts of NPY are included in the culture medium, IC50 5 0.2 nM. Treatment with pertussis toxin completely prevents the effect of NPY. The rank order of potency for inhibition of tyrosine hydroxylase activity is NPY $ [Leu31,Pro34]NPY $ peptide YY. NPY2–36.NPY13–36. NPY18–36 $ NPY26–36.. NPY1–30, suggesting a NPY-Y