Human pheochromocytomas express orexin receptor type 2 gene and display an in vitro secretory response to orexins A and B

J Clin Endocrinol Metab. 2001 Oct;86(10):4818-21. doi: 10.1210/jcem.86.10.7929.


Orexins A and B are hypothalamic peptides, that act through two receptor subtypes, called OX1-R and OX2-R. OX1-R selectively binds orexin A, whereas OX2-R is nonselective for both orexins. High levels of OX1-R mRNA and low levels of OX2-R mRNA have been previously detected in the human adrenal cortex and medulla. Here we demonstrated by RT-PCR the expression of the OX2-R, but not the OX1-R, gene in 10 benign secreting pheochromocytomas. Both orexins A and B stimulated catecholamine secretion from pheochromocytoma slices; the maximal effective concentration was 10(-8) mol/liter. Orexins A and B (10(-8) mol/liter) increased IP3, but not cAMP production, by tumor slices, and the effect was blocked by the PLC inhibitor U-73122. The catecholamine response to 10(-8) mol/liter orexins A and B was abolished by either U-73122 or the PKC antagonist calphostin C and was unaffected by the adenylate cyclase inhibitor SQ-22536 and the PKA inhibitor H-89. Collectively, these findings suggest that orexins stimulate catecholamine secretion from human pheochromocytomas, acting through OX2-R coupled to the PLC-PKC signaling pathway.

MeSH terms

  • Adrenal Gland Neoplasms / metabolism*
  • Carrier Proteins / pharmacology*
  • Dose-Response Relationship, Drug
  • Estrenes / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Neuropeptides / pharmacology*
  • Orexin Receptors
  • Orexins
  • Pheochromocytoma / metabolism*
  • Protein Kinase C / physiology
  • Pyrrolidinones / pharmacology
  • RNA, Messenger / analysis
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Type C Phospholipases / physiology


  • Carrier Proteins
  • Estrenes
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • Pyrrolidinones
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Protein Kinase C
  • Type C Phospholipases