Mika Scheinin, M.D., Ph.D.
Contact information: Dr. Mika Scheinin, Professor of Pharmacology
Institute of Biomedicine, University of Turku
Mail: Department of Pharmacology, Drug Development and Therapeutics, FI-20014 University of Turku, Finland
Street address:Itäinen Pitkäkatu 4B, Turku
Phone: +358 2 333 7502 (office), +358 40 501 4762 (mobile)
Fax: +358 2 333 7216
GROUP MEMBERS
Postdocs:Saku Ruohonen, Ph.D., Suvi Ruohonen, Ph.D.Graduate students:Susann Björk, M.Sc., Jonne Laurila, M.Sc., Anna Huhtinen, M.Sc. (Eng.), Jussi Posti, M.D., Eva-Maria Birkman, M.Sc., Katariina Pohjanoksa, M.Sc., Ville Ranta-Panula, Ümit Özdogan, M.D.
Technicians:Sanna Tikka, Ulla Uoti
PROJECT DESCRIPTION
The project aims to generate new knowledge on the molecular pharmacology of the three α2-adrenoceptor subtypes, a subfamily of the rhodopsin-like G protein coupled receptors. Such knowledge is important for the targeted development of new subtype-selective α2-adrenoceptor agonists and antagonists. The research methods of the group include molecular cloning, mutagenesis and recombinant expression systems, cell-based functional receptor assays, transgenic animal models and clinical studies. Current research on α2-adrenoceptor subtypes includes the following topics: structural determinants of subtype selectivity, receptor activation mechanisms, receptor trafficking and desensitization, functional cell-based model systems for drug screening, receptor distribution patterns in cells and tissues, receptor functions in transgenic mice, regulation of vascular smooth muscle and human receptor gene polymorphisms.
SELECTED RECENT PUBLICATIONS
• Snapir A, Talke P, Posti J, Huiku M, Kentala E, Scheinin M. Effects of nitric oxide synthase inhibition on α2-adrenoceptor-induced vasoconstriction in healthy human volunteers. Brit J Anaesth. 102:38-46, 2009
• Rinne P, Harjunpää J, Scheinin M, Savontaus E. Blood pressure regulation and cardiac autonomic control in mice overexpressing alpha- and gamma-melanocyte stimulating hormone. Peptides 29:1943-52, 2008• Gentili F, Cardinaletti C, Vesprini C, Ghelfi F, Farande A, Giannella M, Piergentili A, Quaglia W, Laurila JM, Huhtinen A, Scheinin M, Pigini A. α2-Adrenoreceptors profile modulation. 4. From antagonist to agonist behavior. J Med Chem. 51:4289-99, 2008
• Kurnik D, Muszkat M, Sofowora GG, Friedman EA, Dupont WD, Scheinin M, Wood AJ, Stein CM. Ethnic and genetic determinants of cardiovascular response to the selective α2-adrenoceptor agonist dexmedetomidine. Hypertension 51:406-11, 2008
• Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, Scheinin H, Scheinin M, Meriläinen P, Himanen SL, Jääskeläinen S. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand. 52:289-94, 2008
• Savontaus E, Fagerholm V, Rahkonen O, Scheinin M. Reduced blood glucose levels, increased insulin levels and improved glucose tolerance in α2A-adrenoceptor knockout mice. Eur J Pharmacol. 578:359-64, 2008
• Fagerholm V, Scheinin M, Haaparanta M. α2A-Adrenoceptor antagonism increases insulin secretion and synergistically augments the insulinotropic effect of glibenclamide in mice. Brit J Pharmacol. 154:1287-96, 2008
• Huhtinen A, Scheinin M: Expression and characterization of the human α2B-adrenoceptor in a vascular smooth muscle cell line. Eur J Pharmacol. 587:48-56, 2008
• Laurila JM, Xhaard H, Ruuskanen JO, Rantanen MJ, Karlsson HK, Johnson MS, Scheinin M: The second extracellular loop of α2A-adrenoceptors contributes to the binding of yohimbine analogues. Brit J Pharmacol. 151:1293-304, 2007
• Snapir A, Posti J, Kentala E, Koskenvuo J, Hakala K, Tuunanen H, Sundell J, Knuuti J, Scheinin H, Scheinin M: The effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects. Anesthesiology105:902-10, 2006
• Özdoğan ÜK, Lähdesmäki J, Scheinin M. The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the α2A-adrenoceptor gene. Eur J Pharmacol. 529:105-13, 2006
• Ruuskanen JO, Laurila J, Xhaard H, Rantanen V-V, Vuoriluoto K, Wurster S, Marjamäki A, Vainio M, Johnson MS, Scheinin M. Conserved structural, pharmacological and functional properties among the three human and five zebrafish α2-adrenoceptors. Brit J Pharmacol. 144:165-77, 2005
• Björk S, Vainio M, Scheinin M. Uneven cellular expression of recombinant α2A-adrenoceptors in transfected CHO cells results in loss of response in adenylyl cyclase inhibition. Biochim Biophys Acta. 1744:38-46, 2005
• Xhaard H, Nyrönen T, Rantanen VV, Ruuskanen JO, Laurila JM, Salminen T, Scheinin M, Johnson MS. Model structures of α2-adrenoceptors in complex with automatically docked antagonist ligands raise the possibility of interactions dissimilar from agonist ligands. J Struct Biol. 150:126-43, 2005
• Cayla C, Heinonen P, Viikari L, Schaak S, Snapir A, Bouloumié A, Karvonen MK, Pesonen U, Scheinin M, Paris H. Cloning, characterisation and identification of several polymorphisms in the promoter region of the human α2B–adrenergic receptor gene. Biochem Pharmacol. 67:469-78, 2004
• Fagerholm V, Philipp M, Hein L, Scheinin M. [Ethyl-3H]RS-79948-197 α2-adrenoceptor autoradiography - validation in α2-adrenoceptor knockout mice. Eur J Pharmacol. 497:301-9, 2004
• Fagerholm V, Grönroos T, Marjamäki P, Viljanen T, Scheinin M, Haaparanta M. Altered glucose homeostasis in α2A-adrenoceptor knockout mice. Eur J Pharmacol. 505:243-52, 2004
• Lähdesmäki J, Sallinen J, MacDonald E, Scheinin M. α2A-Adrenoceptors are important modulators of the effects of D-amphetamine on startle reactivity and brain monoamines. Neuropsychopharmacology 29:1282-93, 2004
• Mansikka H, Lähdesmäki J, Scheinin M, Pertovaara A. α2A-Adrenoceptors contribute to feedback inhibition of capsaicin-induced hyperalgesia. Anesthesiology 101:185-90, 2004
• Özdogan ÜK, Lähdesmäki J, Mansikka H, Scheinin M. Loss of amitriptyline analgesia in α2A-adrenoceptor deficient mice. Eur J Pharmacol. 485:193-6, 2004
• Özdogan ÜK, Lähdesmäki J, Hakala K, Scheinin M. The involvement of α2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 497:161-71, 2004
• Ruuskanen J, Xhaard H, Marjamäki A, Salaneck E, Salminen T, Yan Y-L, Postlethwait JH, Johnson MS, Larhammar D, Scheinin M. Identification of duplicated fourth α2-adrenergic receptor subtype by cloning and mapping of five receptor genes in zebrafish. Mol Biol Evol. 21:14-28, 2004
RECENT Ph.D. THESES
• Frang, Heini: Structural determinants of α2A-adrenoceptor ligand binding and activation (2002)
• Heinonen, Paula: A three amino acid deletion variant in the α2B-adrenergic receptor: Identification and clinical association studies (2003)
• Snapir, Amir: Involvement of a genetic variation in the human α2B-adrenoceptor in acute coronary events and hypertension (2003)
• Olli-Lähdesmäki, Tuire: Cellular regulation of human α2-adrenoceptors - Studies on receptor targeting, trafficking and signalling (2003)
• Holmberg, Maya: Neuroanatomical studies on α2-adrenoceptors (2003)
• Ge, Huifang: Regulation of intracellular calcium by α2-adrenoceptors (2004)
• Lähdesmäki, Janne: Disturbed brain noradrenergic balance and increased neurobehavioural sensitivity of α2A-adrenoceptor knockout mice (2004)
• Ruuskanen, Jori: Comparative molecular and functional analysis of human and zebrafish α2-adrenoceptors (2005)
• Fagerholm, Veronica: α2A-Adrenoceptor regulation of blood glucose homeostasis in mice(2008)