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 accompanied by a corresponding increase in synthesis. The addition of neuropeptide Y (NPY) to the culture medium prevents the increase in catecholamine synthesis but not secretion. Treatment of chromaffin cells with nicotine produces a concentration-dependent increase in tyrosine hydroxylase activity (IC50 = 1.2 microM) that is reduced if NPY is present during stimulation. Tyrosine hydroxylase activity decreases in a concentration-dependent fashion if increasing amounts of NPY are included in the culture medium, IC50 = 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 > or = [Leu31,Pro34]NPY > or = peptide YY > NPY2-36 > NPY13-36 > NPY18-36 > or = NPY26-36 >> NPY1-30, suggesting a NPY-Y1 receptor subtype. Examination of the effect of NPY on nicotine stimulation of chromaffin cell protein phosphorylation showed that NPY produces a concentration-dependent decrease in a 60-kDa protein, IC50 = 6.4 nM. The effect of NPY is pertussis toxin-sensitive. The rank order of potency is [Leu31,Pro34]NPY > or = NPY >> NPY18-36. Immunoprecipitation confirmed the identity of the 60-kDa protein as tyrosine hydroxylase.
Zheng
J
J
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Zhang
P
P
Hexum
T D
TD
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000096:biosynthesis / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D009478:Neuropeptide Y / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D011233:Precipitin Tests; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D010566:Virulence Factors, Bordetella; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine; D004837:Epinephrine