peptide-yy and Pheochromocytoma

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.

Topics: Adrenal Gland Neoplasms; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aromatic Amino Acid Decarboxylase Inhibitors; Cell Differentiation; Dexamethasone; Dihydroxyphenylalanine; Dose-Response Relationship, Drug; Gastrointestinal Hormones; GTP-Binding Proteins; Hydrazines; Nerve Growth Factors; Neuropeptide Y; PC12 Cells; Peptide Fragments; Peptide YY; Peptides; Pertussis Toxin; Pheochromocytoma; Rats; Structure-Activity Relationship; Virulence Factors, Bordetella

Using a porcine neuropeptide Y directed radioimmunoassay it was shown that acid extracts of human phaeochromocytoma tumour tissue contained a neuropeptide Y-like peptide. Further fractionation and purification of this immunoreactivity showed that this human neuropeptide Y-like immunoreactivity was closely similar in molecular size and separation characteristics to porcine neuropeptide Y. The possible contribution of neuropeptide Y to the hypertension characterizing human phaeochromocytoma is discussed.

Topics: Chromatography, Gel; Cross Reactions; Humans; Nerve Tissue Proteins; Neuropeptide Y; Pancreatic Polypeptide; Peptide YY; Peptides; Pheochromocytoma; Radioimmunoassay; Vasoconstriction