This Article Full Text Full Text (PDF) All Versions of this Article: 146/12/5332    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kano, Y. Articles by Makino, H. Search for Related Content PubMed PubMed Citation Articles by Kano, Y. Articles by Makino, H.

Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells

Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City 700-8558, Japan

Address all correspondence and requests for reprints to: Dr. Fumio Otsuka, Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City 700-8558, Japan. E-mail: fumiotsu{at}md.okayama-u.ac.jp.

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

This article has been cited by other articles:

				H. Otani, F. Otsuka, K. Inagaki, J. Suzuki, T. Miyoshi, Y. Kano, J. Goto, T. Ogura, and H. Makino Aldosterone Breakthrough Caused by Chronic Blockage of Angiotensin II Type 1 Receptors in Human Adrenocortical Cells: Possible Involvement of Bone Morphogenetic Protein-6 Actions Endocrinology, June 1, 2008; 149(6): 2816 - 2825. [Abstract] [Full Text] [PDF]

				T. Miyoshi, F. Otsuka, H. Otani, K. Inagaki, J. Goto, M. Yamashita, T. Ogura, Y. Iwasaki, and H. Makino Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells J. Endocrinol., April 1, 2008; 197(1): 159 - 169. [Abstract] [Full Text] [PDF]

				M. Yamashita, F. Otsuka, T. Mukai, H. Otani, K. Inagaki, T. Miyoshi, J. Goto, M. Yamamura, and H. Makino Simvastatin antagonizes tumor necrosis factor-{alpha} inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway J. Endocrinol., March 1, 2008; 196(3): 601 - 613. [Abstract] [Full Text] [PDF]

				M. Takeda, F. Otsuka, H. Otani, K. Inagaki, T. Miyoshi, J. Suzuki, Y. Mimura, T. Ogura, and H. Makino Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope L{beta}T2 cells J. Endocrinol., July 1, 2007; 194(1): 87 - 99. [Abstract] [Full Text] [PDF]

				H. Otani, F. Otsuka, K. Inagaki, M. Takeda, T. Miyoshi, J. Suzuki, T. Mukai, T. Ogura, and H. Makino Antagonistic effects of bone morphogenetic protein-4 and -7 on renal mesangial cell proliferation induced by aldosterone through MAPK activation Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1513 - F1525. [Abstract] [Full Text] [PDF]

				R. Donn, A. Berry, A. Stevens, S. Farrow, J. Betts, R. Stevens, C. Clayton, J. Wang, L. Warnock, J. Worthington, et al. Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII FASEB J, February 1, 2007; 21(2): 402 - 414. [Abstract] [Full Text] [PDF]

				C. E. Pullar, A. Rizzo, and R. R. Isseroff beta-Adrenergic Receptor Antagonists Accelerate Skin Wound Healing: EVIDENCE FOR A CATECHOLAMINE SYNTHESIS NETWORK IN THE EPIDERMIS J. Biol. Chem., July 28, 2006; 281(30): 21225 - 21235. [Abstract] [Full Text] [PDF]