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Research ArticleArticle

Neuropeptide Y Inhibits Chromaffin Cell Nicotinic Receptor-Stimulated Tyrosine Hydroxylase Activity through a Receptor-Linked G Protein-Mediated Process

Jialin Zheng, Peijin Zhang and Terry D. Hexum
Molecular Pharmacology December 1997, 52 (6) 1027-1033; DOI: https://doi.org/10.1124/mol.52.6.1027
Jialin Zheng
Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6260
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Peijin Zhang
Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6260
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Terry D. Hexum
Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6260
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Abstract

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 μm) 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 ≥ [Leu31,Pro34]NPY ≥ peptide YY > NPY2–36>NPY13–36 > NPY18–36 ≥ 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 ≥ NPY ≫ NPY18–36. Immunoprecipitation confirmed the identity of the 60-kDa protein as tyrosine hydroxylase.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 52 (6)
Molecular Pharmacology
Vol. 52, Issue 6
1 Dec 1997
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Research ArticleArticle

Neuropeptide Y Inhibits Chromaffin Cell Nicotinic Receptor-Stimulated Tyrosine Hydroxylase Activity through a Receptor-Linked G Protein-Mediated Process

Jialin Zheng, Peijin Zhang and Terry D. Hexum
Molecular Pharmacology December 1, 1997, 52 (6) 1027-1033; DOI: https://doi.org/10.1124/mol.52.6.1027

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Research ArticleArticle

Neuropeptide Y Inhibits Chromaffin Cell Nicotinic Receptor-Stimulated Tyrosine Hydroxylase Activity through a Receptor-Linked G Protein-Mediated Process

Jialin Zheng, Peijin Zhang and Terry D. Hexum
Molecular Pharmacology December 1, 1997, 52 (6) 1027-1033; DOI: https://doi.org/10.1124/mol.52.6.1027
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