Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells

Eur J Pharmacol. 1995 Dec 20;287(3):271-7. doi: 10.1016/0014-2999(95)00496-3.

Abstract

In PC12 rat pheochromocytoma cells differentiated with nerve growth factor (NGF), neuropeptide Y inhibited depolarization-stimulated catecholamine synthesis as determined by in situ measurement of 3,4-dihydroxyphenylalanine (DOPA) production in the presence of the decarboxylase inhibitor m-hydroxybenzylhydrazine (NSD-1015). The inhibition by neuropeptide Y was concentration-dependent and was prevented by pretreatment with pertussis toxin, suggesting the involvement of a GTP-binding protein of the Gi or Go subtype. The neuropeptide Y analog [Leu31,Pro34]neuropeptide Y also caused inhibition of DOPA production, but was less potent than neuropeptide Y itself, while peptide YY and neuropeptide Y-(13-36) had no significant effect. This pattern is most consistent with the involvement of the neuropeptide Y Y3 receptor subtype. In PC12 cells differentiated with dexamethasone, neuropeptide Y also caused a concentration-dependent inhibition of DOPA production, while peptide YY was again without effect. Neuropeptide Y had no effect on DOPA production in undifferentiated PC12 cells. These results indicate that neuropeptide Y can modulate catecholamine synthesis in addition to its modulatory effects on catecholamine release.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms / parasitology*
  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aromatic Amino Acid Decarboxylase Inhibitors*
  • Cell Differentiation / drug effects
  • Dexamethasone / pharmacology
  • Dihydroxyphenylalanine / metabolism*
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / metabolism
  • Gastrointestinal Hormones / pharmacology
  • Hydrazines / pharmacology
  • Nerve Growth Factors / pharmacology
  • Neuropeptide Y / analogs & derivatives
  • Neuropeptide Y / pharmacology*
  • PC12 Cells / cytology
  • PC12 Cells / drug effects*
  • Peptide Fragments / pharmacology
  • Peptide YY
  • Peptides / pharmacology
  • Pertussis Toxin
  • Pheochromocytoma / pathology*
  • Rats
  • Structure-Activity Relationship
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Gastrointestinal Hormones
  • Hydrazines
  • Nerve Growth Factors
  • Neuropeptide Y
  • Peptide Fragments
  • Peptides
  • Virulence Factors, Bordetella
  • neuropeptide Y (13-36)
  • Peptide YY
  • neuropeptide Y, Leu(31)-Pro(34)-
  • Dihydroxyphenylalanine
  • Dexamethasone
  • 3-hydroxybenzylhydrazine
  • Pertussis Toxin
  • GTP-Binding Proteins