RRC ID 71709
Author Nanmoku T, Isobe K, Sakurai T, Yamanaka A, Takekoshi K, Kawakami Y, Ishii K, Goto K, Nakai T.
Title Orexins suppress catecholamine synthesis and secretion in cultured PC12 cells.
Journal Biochem Biophys Res Commun
Abstract New orexigenic peptides called orexin-A and -B have recently been described in neurons of the lateral hypothalamus and perifornical area. No orexins have been found in adipose tissues or visceral organs, including the adrenal gland. However, expression of the orexin-receptor 2 (OX2R) in the rat adrenal gland has been reported. To test the effects of orexins on peripheral organs, we investigated their effects on catecholamine synthesis and secretion in the rat pheochromocytoma cell line PC12. Orexin-A and -B (100 nM) significantly reduced basal and PACAP-induced tyrosine hydroxylase (TH) (the rate-limiting enzyme in the biosynthesis of catecholamines) mRNA levels. Orexin-A and -B (100 nM) also significantly inhibited the PACAP-induced increase in the cAMP level, suggesting that the suppressive effect on TH mRNA is mediated, at least in part, by the cAMP/protein kinase A pathway. Furthermore, orexin-A and -B (100 nM) significantly suppressed basal and PACAP-induced dopamine secretion from PC12 cells. Next, we examined whether orexin receptors (OX1R, OX2R) were present in the rat adrenal gland and PC12 cells. In the adrenal glands, OX2R was as strongly expressed as in the hypothalamus, but OX1R was not detected. On the other hand, neither OX1R nor OX2R was expressed in PC12 cells. However, binding assays showed equal binding of orexin-A and -B to PC12 cells, suggesting the existence in these cells of some receptors for orexins. These results indicate that orexins suppress catecholamine release and synthesis, and that the inhibitory effect is mediated by the cAMP/protein kinase A pathway.
Volume 274(2)
Pages 310-5
Published 2000-8-2
DOI 10.1006/bbrc.2000.3137
PII S0006-291X(00)93137-1
PMID 10913336
MeSH Adrenal Gland Neoplasms / metabolism* Adrenal Gland Neoplasms / pathology Animals Binding, Competitive / drug effects Calcium / metabolism Carrier Proteins / metabolism* Carrier Proteins / pharmacology Cyclic AMP / biosynthesis Dopamine / biosynthesis* Dopamine / metabolism* Dose-Response Relationship, Drug Intracellular Signaling Peptides and Proteins* Neuropeptides / metabolism* Neuropeptides / pharmacology Neurotransmitter Agents / metabolism Neurotransmitter Agents / pharmacology Orexin Receptors Orexins PC12 Cells Pheochromocytoma / metabolism* Pheochromocytoma / pathology Pituitary Adenylate Cyclase-Activating Polypeptide RNA, Messenger / biosynthesis Rats Receptors, G-Protein-Coupled Receptors, Neuropeptide / biosynthesis Tyrosine 3-Monooxygenase / genetics Tyrosine 3-Monooxygenase / metabolism
IF 2.985
Human and Animal Cells PC-12(RCB0009)