研究業績

2020年

Makino T, Kagoyama K, Murabe C, Nakamura T, Shimizu T. Association of Development of Solar Elastosis with Increased Expression of Fibrillin-1, LTBP-2 and Fibulin-4 in Combination with Decreased Expression of LTBP-4. Acta Derm Venereol 101(1):adv00372, 2021.    

Noda K, Kitagawa K, Miki T, Horiguchi M, Akama TO, Taniguchi T, Taniguchi H, Takahashi K, Ogra Y, Mecham RP, Terajima M, Yamauchi Y, Nakamura T: A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase. Sci Adv 6(48):eabc1404, 2020. doi: 10.1126/sciadv.abc1404.    

Nakamura T, Bornstein P: Matricellular Proteins. Book Chapter in Reference Module in Biomedical Sciences 2020. doi: 10.1016/b978-0-08-102723-3.00009-3.    

Kinoshita Y, Ikeda T, Kushima H, Fujita M, Nakamura T, Nabeshima K, Ishii H: Serum latent transforming growth factor-β binding protein 4 as a novel biomarker for idiopathic pleuroparenchymal fibroelastosis. Respir Med 171:106077, 2020.    


2019年

Koyama S, Horie T, Nishino T, Baba O, Sowa N, Miyasaka Y, Kuwabara Y, Nakao T, Nishiga M, Nishi H, Nakashima Y, Nakazeki F, Ide Y, Kimura M, Tsuji S, Ruiz Rodriguez R, Xu S, Yamasaki T, Otani C, Watanabe T, Nakamura T, Hasegawa K, Kimura T, Ono K. Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice. J Am Heart Assoc 8(13):e012609, 2019.    

Mori H, Yamada H, Toyama K, Takahashi K, Akama T, Inoue T, Nakamura T: Developmental and age-related changes to the elastic lamina of Bruch's membrane in mice. Graefes Arch Clin Exp Ophthalmol 257(2):289-301, 2019.    


2018年

Nishino T, Horie T, Baba O, Sowa N, Hanada R, Kuwabara Y, Nakao T, Nishiga M, Nishi H, Nakashima Y, Nakazeki F, Ide Y, Koyama S, Kimura M, Nagata M, Yoshida K, Takagi Y, Nakamura T, Hasegawa K, Miyamoto S, Kimura T, Ono K: SREBF1/MicroRNA-33b Axis Exhibits Potent Effect on Unstable Atherosclerotic Plaque Formation In Vivo. Arterioscler Thromb Vasc Biol 38(10):2460-2473, 2018.    

Yamashiro Y, Thang BQ, Shin SJ, Lino CA, Nakamura T, Kim J, Sugiyama K, Tokunaga C, Sakamoto H, Osaka M, Davis EC, Wagenseil JE, Hiramatsu Y, Yanagisawa H: Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans. Circ Res 31;123(6):660-672, 2018.    

Nakamura T: Roles of short fibulins, a family of matricellular proteins, in lung matrix assembly and disease. Matrix Biol 73C:21-33, 2018. 

   

2017年

Bultmann-Mellin I, Dinger K, Debuschewitz C, Loewe KMA, Melcher Y, Plum MTW, Appel S, Rappl G, Willenborg S, Schauss AC, Jüngst C, Krüger M, Dressler S, Nakamura T, Wempe F, Alejandre Alcázar MA, Sterner-Kock A: Role of LTBP-4 in alveolarization, angiogenesis and fibrosis in lungs. Am J Physiol Lung Cell Mol Physiol 313(4):L687-L698, 2017.    

Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K: MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol. Circ Res 120(5):835-847, 2017.   

Fujikawa Y, Yoshida H, Inoue T, Ohbayashi T, Noda K, von Melchner H, Iwasaka T, Shiojima I, Akama TO, Nakamura T: Latent TGF-β binding protein 2 and 4 have essential overlapping functions in microfibril development. Sci Rep 7:43714, 2017. 

   

2016年

Kageshima M, Maruyama T, Akama T, Nakamura T: Novel magnetic indenter for rheological analysis of thin biological sheet for regenerative medicine. Rev Sci Instrum 87:074302, 2016. 


2015年

Nakasaki M, Hwang Y, Xie Y, Kataria S, Gund R, Hajam EY, Samuel R, George R, Danda D, M J P, Nakamura T, Shen Z, Briggs S, Varghese S, Jamora C: The matrix protein Fibulin-5 is at the interface of tissue stiffness and inflammation in fibrosis. Nat Commun 6:8574, 2015. 

Noda K, Nakamura T, Komatsu Y: Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice. Biochem Biophys Res Commun 466:585-91, 2015. 

Aya R, Ishiko T, Noda K, Yamawaki S, Sakamoto Y, Tomihata K, Katayama Y, Yoshikawa K, Kubota H, Nakamura T, Naitoh M, Suzuki S: Regeneration of elastic fibers by three-dimensional culture on a collagen scaffold and the addition of latent TGF-β binding protein 4 to improve elastic matrix deposition. Biomaterials 72:29-37, 2015. 

Fanhchaksai K, Okada F, Nagai N, Pothacharoen P, Kongtawelert P, Hatano S, Makino S, Nakamura T, Watanabe H: Host stromal versican is essential for cancer-associated fibroblast function to inhibit cancer growth. Int J Cancer 138:630-41, 2016. 

Bultmann-Mellin I, Conradi A, Maul AC, Dinger K, Wempe F, Wohl AP, Imhof T, Wunderlich FT, Bunck AC, Nakamura T, Koli K, Bloch W, Ghanem A, Heinz A, von Melchner H, Sengle G, Sterner-Kock A: Modeling autosomal recessive cutis laxa type 1C (ARCL1C) in mice reveals distinct functions of Ltbp-4 isoforms. Dis Model Mech 8:403-415, 2015. 

Endo T, Nakamura J, Sato Y, Asada M, Yamada R, Takase M, Takaori K, Oguchi A, Iguchi T, Higashi AY, Ohbayashi T, Nakamura T, Muso E, Kimura T, Yanagita M. Exploring the origin and limitations of kidney regeneration. J Pathol 236:251-263, 2015.


2014年

Inoue T, Ohbayashi T, Fujikawa Y, Yoshida H, Akama TO, Noda K, Horiguchi M, Kameyama K, Hata Y, Takahashi K, Kusumoto K, Nakamura T: Latent TGFβ binding protein-2 is essential for the development of ciliary zonule microfibrils. Hum Mol Genet 23:5672-82, 2014.

Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Nakazeki F, Ide Y, Koyama S, Sowa N, Yahagi N, Shimano H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K: MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo. Sci Rep 4:5312, 2014.

Yokoyama U, Minamisawa S, Shioda A, Ishiwata R, Jin MH, Masuda M, Asou T, Sugimoto Y, Aoki H, Nakamura T, Ishikawa Y: Prostaglandin E2 inhibits elastogenesis in the ductus arteriosus via EP4 signaling. Circulation129:487-96, 2014.


2013年

Noda K, Dabovic B, Takagi K, Inoue T, Horiguchi M, Hirai M, Fujikawa Y, Akama TO, Kusumoto K, Zilberberg L, Sakai LY, Koki K, Naitoh M, von Melchner H, Suzuki S, Rifkin DB, Nakamura T: Latent TGFβ binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5.  Proc Natl Acad Sci USA 110:2852-7, 2013.

Saito R, Shirakawa R, Nishiyama H, Kobayashi T, Kawato M, Kanno T, Nishizawa K, Matsui Y, Ohbayashi T, Horiguchi M, Nakamura T, Ikeda T, Yamane K, Nakayama E, Nakamura E, Toda Y, Kimura T, Kita T, Ogawa O, Horiuchi H: Downregulation of Ral GTPase-activating protein promotes tumor invasion and metastasis of bladder cancer. Oncogene 32:894-902, 2013.


2012年

Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K: MicroRNA-33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE(-/-) Mice. J Am Heart Assoc 2012 Dec;1(6):e003376. doi: 10.1161/JAHA.112.003376. Epub 2012 Dec 19.    


2011年

Otani H, Yoshioka K, Nishikawa H, Inagaki C, Nakamura T: Involvement of Protein Kinase C and RhoA in Protease-Activated Receptor 1-Mediated F-Actin Reorganization and Cell Growth in Rat Cardiomyocytes. J Pharmacol Sci 115:135-43, 2011.

Ohara H, Akatsuka S, Nagai H, Liu Y, Jiang L, Okazaki Y, Yamashita Y, Nakamura T, Toyokuni S: Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats. Free Radic Res 45:211-20, 2011.


2010年

Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T: MicroRNA-33 encoded by an intron of Srebp2 regulates HDL in vivo. Proc Natl Acad Sci USA 107:17321-6, 2010.

Lu J, Gong D, Choong SY, Xu H, Chan YK, Chen X, Fitzpatrick S, Glyn-Jones S, Zhang S, Nakamura T, Ruggiero K, Obolonkin V, Poppitt SD, Phillips AR, Cooper GJ: Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal- targeted treatments. Diabetologia 53:1217-26, 2010.


2009年

Horiguchi M, Inoue T, Ohbayashi T, Hirai M, Noda K, Marmorstein LY, Yabe D, Takagi K, Akama TO, Kita T, Kimura T, Nakamura T: Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase. Proc Natl Acad Sci USA  106:19029-34, 2009.

Ikeda M, Naitoh M, Kubota H, Ishiko T, Yoshikawa K, Yamawaki S, Kurokawa M, Utani A, Nakamura T, Nagata K, Suzuki S: Elastic fiber assembly is disrupted by excessive accumulation of chondroitin sulfate in the human dermal fibrotic disease, keloid. Biochem Biophys Res Commun, 390:1221-8, 2009.

Xiong ZM, Kitagawa K, Nishiuchi Y, Kimura T, Nakamura T, Inagaki C.: Acetyl-Ile-Gly-Leu protects neurons from Aß (1-42) induced toxicity in vitro and in V337M human tau-expressing mice. Life Sci 84(5-6):132-8, 2009.


2008年

Yang L, Nakayama Y, Hattori N, Liu B, Inagaki C: GABAc-Receptor Stimulation Activates cAMP-Dependent Protein Kinase via A-Kinase Anchoring Protein 220. J Pharmacol Sci 106:578-584, 2008.

Hattori N, Nakayama Y, Kitagawa K, Ishihara T, Saiki Y, Inagaki C: Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia. Clin Endocrinol 68:72-76, 2008.


2007年

Hirai M, Horiguchi M, Ohbayashi T, Kita T, Chien KR, Nakamura T: Latent TGF-ß binding protein 2 binds to DANCE/fibulin-5 and regulates elastic fiber assembly. EMBO J  26:3283-3295, 2007.

Hirai M, Ohbayashi T, Horiguchi M, Okawa K, Hagiwara A, Kita T, Chien KR, Nakamura T: Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. J Cell Biol 176:1061-1071, 2007.

Hattori N, Nakayama Y, Kitagawa K, Li T, Inagaki C: Development of anti-PRL (prolactin) autoantibodies by homologous PRL in rats: a model for macroprolactinemia. Endocrinology 148:2465-70 2007.

Ando S, Otani H, Yagi Y, Kawai K, Araki H, Nakamura T, Fukahara S, Inagaki C: Protease-activated receptor 4-mediated Ca2+ signaling in mouse lung alveolar epithelial cells. Life Sci 81:794-802, 2007.

Ando S, Otani H, Yagi Y, Kawai K, Araki H, Fukuhara S, Inagaki C: PAR4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells. Respiratory Res 8:31-45, 2007.

Xiong ZM, Kitagawa K, Nishiuchi Y, Kimura T, Inagaki C: Protective effects of Aß-derived tripeptide, Aß32–34, on Aß1–42-induced phosphatidylinositol 4-kinase inhibition and neurotoxicity. Neurosci Lett 419: 247-252, 2007.

Zhang NY, Kitagawa K, Hattori N, Nakayama Y, Xiong ZM, Wu B, Liu B, Inagaki C: Soybean-derived phosphatidylinositol inhibits in vivo low concentrations of amyloid ß protein-induced degeneration of hippocampal neurons in V337M human tau-expressing mice. Life Sci 80:1971-1976, 2007.

Li T, Nakayama Y, Kitagawa K, Hattori N, Xiong ZM, Inagaki C: Down-regulation of Cl- pump ClP55 subunit induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons. Brain Res 1130:235-8, 2007.

 

2006年

Lotery AJ, Baas D, Ridley C, Jones RP, Klaver CC, Stone E, Nakamura T, Luff A, Griffiths H, Wang T, Bergen AA, Trump D: Reduced secretion of fibulin 5 in age-related macular degeneration and cu Hum Mutattis laxa. 27:568-74, 2006.

McLaughlin PJ, Chen Q, Horiguchi M, Starcher BC, Stanton JB, Broekelmann TJ, Marmorstein AD, McKay B, Mecham R, Nakamura T, Marmorstein LY: Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. Mol Cell Biol 26:1700-9, 2006.

Hattori N, Nakayama Y, Kitagawa K, Ishihara T, Saiki Y, Inagaki C: Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia. J Endocrinol 190:287-93, 2006.

Nakayama Y, Hattori N, Otani H, Inagaki C: Gamma-aminobutyric acid (GABA)-C receptor stimulation increases prolactin (PRL) secretion in cultured rat anterior pituitary cells. Biochem Pharmacol 71:1705-10, 2006.

Yagi Y, Otani H, Ando S, Oshiro A, Kawai K, Nishikawa H, Araki H, Fukuhara S, Inagaki C: Involvement of Rho signaling in PAR2-mediated regulation of neutrophil adhesion to lung epithelial cells. Eur J Pharmacol 536:19-27, 2006.

Zhang NY, Kitagawa K, Wu B, Xiong ZM, Otani H, Inagaki C: Chloride-dependency of amyloid beta protein-induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett 399:175-80, 2006.

Wu B, Kitagawa K, Liu B, Zhang NY, Xiong ZM, Inagaki C: Attenuation of amyloid ß (Aß)-induced inhibition of phosphatidylinositol 4-kinase activity by Aß fragments, Aß20-29 and Aß31-35. Neurosci Lett 396:148-52, 2006.

 

2005年

Liu B, Hattori N, Zhang NY, Wu B, Yang L, Kitagawa K, Xiong ZM, Irie T, Inagaki C: Anxiolytic agent, dihydrohonokiol-B, recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett 384:44-7, 2005.

Sumita K, Hattori N, Inagaki C: Effects of growth hormone on the differentiation of mouse B-lymphoid precursors. J Pharmacol Sci 97:408-16, 2005.

Hattori N, Ikekubo K, Nakaya Y, Kitagawa K, Inagaki C: Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies. J Clin Endocrinol Metab 90:3036-44, 2005.

 

2004年

Pradervand S, Yasukawa H, Muller OG, Kjekshus H, Nakamura T, St Amand T, Yajima T, Matsumura K, Duplain H, Iwatate M, Woodard S, Pedrazzini T, Ross J, Firsov D, Rossier BC, Hoshijima M, Chien KR: Small proline-rich protein 1A is a gp130 pathway and stress inducible cardio-protective protein. EMBO J 23: 4517-25, 2004.

Wu B, Kitagawa K, Zhang NY, Liu B, Inagaki C: Pathophysiological concentrations of amyloid beta proteins directly inhibit rat brain and recombinant human type II phosphatidylinositol 4-kinase activity. J Neurochem 91:1164-70, 2004.

Iwata R, Kitagawa K, Zhang NY, Wu B, Inagaki C: Non-steroidal anti-inflammatory drugs protect amyloid beta protein-induced increase in the intracellular Cl- concentration in cultured rat hippocampal neurons. Neurosci Lett 367:156-9, 2004.

Jiang B, Hattori N, Liu B, Nakayama Y, Kitagawa K, Sumita K, Inagaki C: Expression and roles of Cl- channel ClC-5 in cell cycles of myeloid cells. Biochem Biophys Res Commun 317:192-7, 2004.

Liu B, Hattori N, Jiang B, Nakayama Y, Zhang NY, Wu B, Kitagawa K, Taketo M, Matsuda H, Inagaki C: Single cell RT-PCR demonstrates differential expression of GABAC receptor rho subunits in rat hippocampal pyramidal and granule cells. Brain Res Mol Brain Res 123:1-6, 2004.

Jiang B, Hattori N, Liu B, Nakayama Y, Kitagawa K, Inagaki C: Suppression of cell proliferation with induction of p21 by Cl(-) channel blockers in human leukemic cells. Eur J Pharmacol 488:27-34, 2004.

Oshiro A, Otani H, Yagi Y, Fukuhara S, Inagaki C: Protease-activated receptor-2-mediated inhibition for Ca2+ response to lipopolysaccharide in Guinea pig tracheal epithelial cells. Am J Respir Cell Mol Biol 30:886-92, 2004.

 

2003年

Yasukawa H, Yajima T, Duplain H, Iwatate M, Kido M, Hoshijima M, Weitzman MD, Nakamura T, Woodard S, Xiong D, Yoshimura A, Chien KR, Knowlton KU: The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin Invest 111: 469-478, 2003.

Yang L, Omori K, Omori K, Otani H, Suzukawa J, Inagaki C: GABAC receptor agonist suppressed ammonia-induced apoptosis in cultured rat hippocampal neurons by restoring phosphorylated BAD level. J Neurochem 87:791-800, 2003.

Zhang NY, Kitagawa K, Wu B, Inagaki C: Soybean-derived phosphatidylinositol recovers amyloid beta protein-induced neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett 350:105-8, 2003.

 

2002年

Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, Cheng C, Kobuke K, Dalton N, Takada Y, Tashiro K, Ross Jr. J, Honjo T, Chien KR: Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415: 171-175, 2002.

Yagyu K, Kitagawa K, Wu B, Zhang NY, Irie T, Hattori N, Inagaki C: Protective effects of estradiol against amyloid beta protein-induced inhibition of neuronal Cl(-)-ATPase activity. Neuropharmacology 43:1297-304, 2002.

Wu B, Kitagawa K, Yagyu K, Zhang NY, Hattori N, Inagaki C: Phosphatidylinositol and PI-4-monophosphate recover amyloid beta protein-induced inhibition of Cl- -ATPase activity. Life Sci 72:455-63, 2002.

Oshiro A, Otani H, Yagi Y, Fukuhara S, Inagaki C: Protease-activated receptor-2-mediated Ca2+ signaling in guinea pig tracheal epithelial cells. Life Sci 71:547-58, 2002.

Jiang B, Hattori N, Liu B, Kitagawa K, Inagaki C: Expression of swelling- and/or pH-regulated chloride channels (ClC-2, 3, 4 and 5) in human leukemic and normal immune cells. Life Sci 70:1383-94, 2002.

 

2001年

Yasukawa H, Hoshijima H, Gu Y, Nakamura T, Pradervand S, Hanada T, Hanakawa Y, Yoshimura A, Ross Jr. J, Chien KR: Suppressor of cytokine signal-3 is a biomechanical stress inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways. J Clin Invest 108: 1549-1567, 2001.

Kinoshita M, Nakamura T, Ihara M, Haraguchi T, Hiraoka Y, Tashiro K, Noda M: Identification of human endomucin-1 and -2 as membrane-bound O-sialoglycoproteins with anti-adhesive activity. FEBS Lett 499: 121-126, 2001.

Kitagawa K, Yagyu K, Yamamoto A, Hattori N, Omori K, Zeng XT, Inagaki C: Molecular cloning and characterization of the Cl(-) pump-associated 55-kDa protein in rat brain. Biochem Biophys Res Commun 289:363-71, 2001.

Irie T, Miyamoto E, Kitagawa K, Maruyama Y, Inoue K, Inagaki C: An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl(-) of cultured rat hippocampal neurons via GABA(c) receptors. Neurosci Lett 312:121-3, 2001.

Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C: GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 86:4284-91, 2001.

Yagyu K, Kitagawa K, Irie T, Wu B, Zeng XT, Hattori N, Inagaki C: Amyloid beta proteins inhibit Cl(-)-ATPase activity in cultured rat hippocampal neurons. J Neurochem 78:569-76, 2001.

Otani H, Oshiro A, Yagi M, Inagaki C: Pertussis toxin-sensitive and -insensitive mechanisms of alpha1-adrenoceptor-mediated inotropic responses in rat heart. Eur J Pharmacol 419:249-52, 2001.

Mishima K, Otani H, Tanabe T, Kawasaki H, Oshiro A, Saito N, Ogawa R, Inagaki C: Molecular mechanisms for alpha2-adrenoceptor-mediated regulation of synoviocyte populations. Jpn J Pharmacol 85:214-26, 2001.

Zeng XT, Mikami-Uriu T, Higashida T, Yagyu K, Kitagawa K, Hattori N, Otani H, Omori K, Inagaki C: Developmental changes in Cl(-)-ATPase activity in rat brains. Neurosci Lett 302:101-4, 2001.

Inagaki C, Hattori N, Kitagawa K, Zeng XT, Yagyu K: Cl(-)-ATPase in rat brain and kidney. J Exp Zool 289:224-31, 2001.

Kawasaki H, Otani H, Mishima K, Imamura H, Inagaki C: Involvement of anion exchange in the hypoxia/reoxygenation-induced changes in pH(i) and [Ca2+]i in cardiac myocytes. Eur J Pharmacol 411:35-43, 2001.