Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells.
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.
McCullough
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LA
Department of Pharmacological and Physiological Science, Saint Louis University Health Sciences Center, MO 63104, USA.
Westfall
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TC
D000310:Adrenal Gland Neoplasms / Q000469:parasitology*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D010673:Pheochromocytoma / Q000473:pathology*; D051381:Rats; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D005768:Gastrointestinal Hormones; D006834:Hydrazines; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D010566:Virulence Factors, Bordetella; C062924:neuropeptide Y (13-36); D019894:Peptide YY; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D004295:Dihydroxyphenylalanine; D003907:Dexamethasone; C004297:3-hydroxybenzylhydrazine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins