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

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 corte...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2001-10, Vol.86 (10), p.4818-4821
Main Authors: MAZZOCCHI, G, MALENDOWICZ, L. K, ARAGONA, F, REBUFFAT, P, GOTTARDO, L, NUSSDORFER, G. G
Format: Article
Language:English
Subjects:
Adrenal Gland Neoplasms - metabolism
Adrenals. Adrenal axis. Renin-angiotensin system (diseases)
Biological and medical sciences
Carrier Proteins - pharmacology
Dose-Response Relationship, Drug
Endocrinopathies
Estrenes - pharmacology
Humans
Intracellular Signaling Peptides and Proteins
Medical sciences
Neuropeptides - pharmacology
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Orexin Receptors
Orexins
Pheochromocytoma - metabolism
Protein Kinase C - physiology
Pyrrolidinones - pharmacology
Receptors, G-Protein-Coupled
Receptors, Neuropeptide - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Type C Phospholipases - physiology
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Summary: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.86.10.4818