Ruta MUCENIECE

Ruta MUCENIECE, Ph.D Associate professor Faculty of Medicine University of Latvia Sarlotes iela 1a Riga, LV-1001 Latvia Phone: (371) 67362499 Fax: (371) 67366306 e-mail: [email protected]

Born: March 24, 1950, Latvia

• G-protein-coupled receptors
• Melanocortins
• Pharmacy education

Main research field - studies of melanocortin receptors.

Languages: Latvian, Russian, English, Swedish

• Master's degree in Pharmacy, Riga Medical Academy (Faculty of Pharmacy), 1976
• Dr.biol. (Candidate of Sciences in former USSR system), Tartu University, Estonia, 1982

                Thesis: “Short peptide influence on the brain monoaminergic processes”.

• Dr. habil. biol., University of Latvia, 1999

                Thesis: “Melanocortin receptors: from cloning to selective ligands”

Postdoctoral Research Training -

• Postdoctoral Fellowship, Pathophysiological Institute, Szeged University, Hungary, 1987 (1 month)
• Visiting Researcher, Department of Pharmacology, Umeå University, Sweden , 1992
• Visiting Researcher, Department of Pharmaceutical Pharmacology, Biomedical Centre, Uppsala University, Sweden, 1993-2000
• Visiting Researcher, Laboratoire de Chimie et Biochimie Pharmaacoogiques et Toxicologiques, Paris University CNRS UMR 8601, France, 2003.

• Senior Researcher, Head of Neurochemistry Group, Institute of Organic Synthesis, Riga, Latvia, 1987-1999
• Associate Professor, Director of Pharmacy Program, University of Latvia, 2000 - 2005
• Professor, Director of Pharmacy Program, University of Latvia,  2005 -

• Corresponding Member, Latvian Academy of Sciences, 2001
• Swedish Institute Fellowship, Program of a2-Adrenoreceptor and Idazoxan Receptor Studies, 1992 (6 months)
• Procordia Executive Committee Fellowship, Program of Research Fellowships in Molecular Biology (Studies of DNAs-sequencing methods, cloning, expression of MSH receptor subtypes), 1993-1995
• STINT Fellowship, Program of Molecular Pharmacology of Selective Melanocortin Receptor Ligands, 1997 (4 months)
• NOVO NORDISK A/S Fellowship, Program of Optimisation of Receptor Protein Expression in the SF9 Cells, 1999-2000
• The L'Oreal-Unesco for Women in Science Award (Latvia, together with LAS), 2005
• D. H. Grindel Medal (Company “Grindex”, Latvia), 2007

• Responsible person for a 10 credit elective course in molecular pharmacology, Faculty of Pharmacy, Uppsala University, Sweden, 1996-2000
• Director of Pharmacy Program, University of Latvia, 2000 -

• Member, Latvian Society of Pharmacologists

Recent/Representative Publications (after 1993) 

• Muceniece R, Zvejniece L, Vilskersts R, Liepinsh E, Baumane L, Kalvinsh I, Wikberg JE, Dambrova M. Functional Evaluation of THIQ, a Melanocortin 4 Receptor Agonist, in Models of Food Intake and Inflammation. - Basic Clin Pharmacol Toxicol.,  2007 Dec, vol. 101, N 6, pp. 416-20. PMID: 18028105 [PubMed - in process]
• Mutulis F, Kreicberga J, Yahorava S, Mutule I, Borisova-Jan L, Yahorau A, Muceniece R, Azena S, Veiksina S, Petrovska R, Wikberg JE. Design and synthesis of a library of tertiary amides: evaluation as mimetics of the melanocortins' active core.- Bioorg Med Chem.,   2007 Sep 1;vol. 15, N 17, pp. 5787-5810. PMID: 17618123 [PubMed - indexed for MEDLINE]
• Muceniece R, Saleniece K, Riekstina U, Krigere L, Tirzitis G, Ancans J. Betulin binds to melanocortin receptors and antagonizes alpha-melanocyte stimulating hormone induced cAMP generation in mouse melanoma cells. - Cell Biochem Funct.,  2007 Sep-Oct; vol. 25, N 5, pp.591-596.
• Schioth HB, Muceniece R, Mutule I,  Wikberg JE. New melanocortin 1 receptor binding motif based on the C-terminal sequence of alpha-melanocyte-stimulating hormone - Basic Clin. Pharmacol. Toxicol., 2006, N 4, pp. 287-293.
• Muceniece R, Zvejniece L, Liepinsh E, Kirjanova O, Baumane L, et al. The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model. - Peptides, 2006, vol. 27, N6, pp. 1443-1450.
• Jansone B., Muceniece R., Klusa V., Svirskis S., Petrovska R., Duburs G., Wikberg J.E. The non-peptide compound cerebrocrast is a highly selective melanocortin MC4 receptor agonist and inhibits feeding. - Proc. Latv. Acad. Sci., B, 2004, vpl. 58, pp. 98-103.
• Muceniece R, Zvejniece L, Kirjanova O, Liepinsh E, Krigere L, Baumane L, Kalvinsh I, Wikberg JE, Dambrova M.  ß- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain. - Brain Res.,  2004,   995, N 1, pp.  7-13. PMID: 14644465 [PubMed - in process]
• Dambrova M, Kirjanova O, Baumane L, Liepinsh E, Zvejniece L, Muceniece R, Kalvinsh I, Wikberg JE. EPR investigation of in vivo inhibitory effect of guanidine compounds on nitric oxide production in rat tissues. - J.Physiol. Pharmacol., 2003, vol. 54, N 3, pp. 339-347. PMID: 14566073 [PubMed - in process]
• Muceniece R, Krigere L, Suli-Vargha H, Wikberg JE. Effects of alpha-melanotropin C-terminal tripeptide analogues on macrophage NO production. - Peptides, 2003, vol. 24, N 5, pp. 701-707.PMID: 12895656 [PubMed - in process]
• Schioth HB, Kask A, Mutulis F, Muceniece R, Mutule I, Mutule I, Mandrika I, Wikberg JE Novel selective melanocortin 4 receptor antagonist induces food intake after peripheral administration. - Biochem. Biophys. Res. Commun., 2003, vol. 301, N 2, pp. 399-405. PMID: 12895656 [PubMed -   indexed for MEDLINE]
• Schioth HB, Tesafaye A, Mutulis F, Rudzish R,  Mutule I, Muceniece R, Watanobe H, Wikberg JE. Subtype selective binding properties of substituted linear melanocyte stimulating hormone analogues. - Neuropeptides, 2002,  vol. 36, N 6, pp. 427-434. PMID: 12507437 [PubMed - in process]
• Schioth HB, Bouifrouri AA, Rudzish R, Muceniece R, Watanobe H, Wikberg JE, Larhammar D. Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in vitro.- Regul Pept., 2002, vol. 106, N 1-3, pp. 7-12. PMID: 12047904 [PubMed - indexed for MEDLINE]
• Neumann Andersen G, Nagaeva O, Mandrika I, Petrovska R, Muceniece R, Mincheva-Nilsson L, Wikberg JE. MC(1) receptors are constitutively expressed on leucocyte subpopulations with antigen presenting and cytotoxic functions.- Clin. Exp. Immunol.,  2001 , vol.126, N 3, pp. 441-446. PMID: 11737060 [PubMed - indexed for MEDLINE]
• Schioth HB, Tesfaye A, Mutulis F, Rudzish R, Mutule I, Muceniece R, Watanobe H, Wikberg JE. Subtype selective binding properties of substituted linear melanocyte stimulating hormone analogues. - Neuropeptides,   2002, vol. 36, N 6, pp. 427-434.
• Mandrika I., Muceniece R.,Wikberg J.E.S. Effects of malanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7: evidence for dual mechanisms of action. - Biochem. Pharmacol., 2001, vol. 61, pp. 613-621.
• P.Prusis, R.Muceniece, I.Mutule,  F.Mutulis,  J.E..Wikberg. Design of new small cyclic melanocortin receptor-binding peptides using molecular modelling: Role of the His residue in the melanocortin peptide core. - Eur. J.Med.Chem., 2001, vol. 36, pp.137-146.
• P.Prusis, R.Muceniece, P.Anderson, C.Post, T.Lunstedt, J.E.S.Wikberg. PLS modelling of chimeric MS04/MSH-peptide and MC1/MC3-receptor interactions reveals a novel method for the analysis of ligand-receptor interactions. - BBA, 2001; 1544, pp. 35-37.
• R.Muceniece, I.Mutule,  F.Mutulis, P.Prusis, M.Szardenings, J.E.S.Wikberg.Detection of regions in the MC1 receptor of importance for the selectivity of the MC1 receptor super-selective MS04/MS05 peptides. - BBA, 2001; 1544, pp. 278-282.
• Wikberg J.E.S., Muceniece R., Mandrika I., Prusis P., Lindblom J., Post C., Skottner A. New aspects on the melanocortin and their receptors. - Pharmacol. Res., 2000, vol. 42, pp. 393-420.
• Szardenings M, Muceniece R, Mutule I, Mutulis F, Wikberg JE. New highly specific agonistic peptides for human melanocortin MC(1) receptor. - Peptides, 2000, vol. 21(2), pp. 239-243.
• Schioth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE. Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. - Neuropeptides, 1999, vol. 33(3), pp.191-196.
• Klusa V, Svirskis S, Opmane B, Muceniece R, Wikberg JE. Behavioural responses of gamma-MSH peptides administered into the rat ventral tegmental area. - Acta Physiol. Scand., 1999, vol.167(2), pp. 99-104.
• Schioth HB, Prusis P, Muceniece R, Mutulis F, Mutule I, Wikberg JE. Thyrotropin releasing hormone (TRH) selectively binds and activates the melanocortin 1 receptor. - Peptides, 1999, vol. 20(3), pp. 395-400.
• Skuladottir GV, Jonsson L, Skarphedinsson JO, Mutulis F, Muceniece R, Raine A, Mutule I, Helgason J, Prusis P, Wikberg JE, Schioth HB. Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist. - Br. J. Pharmacol., 1999, vol. 126(1), pp. 27-34.
• Klusa V, Svirskis S, Opmane B, Muceniece R, Skujins A, Mutulis F, Wikberg JE, Schioth HB.Evaluation of behavioural effects of neural melanocortin receptor antagonists injected ICV and in VTA in rats. - Neuropeptides, 1998 vol. 32(6), pp. 573-580.
• Kask A, Mutulis F, Muceniece R, Pahkla R, Mutule I, Wikberg JE, Rago L, Schioth HB. Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. - Endocrinology, 1998, vol. 139(12), pp. 5006-5014.
• Schioth HB, Fredriksson A, Carlsson C, Yook P, Muceniece R, Wikberg JE. Evidence indicating that the extracellular loops of the mouse MC5 receptor do not participate in ligand binding. - Mol. Cell Endocrinol., 1998, vol.139(1-2), pp.109-115.
• Schioth HB, Mutulis F, Muceniece R, Prusis P, Wikberg JE. Selective properties of C- and N-terminals and core residues of the melanocyte-stimulating hormone on binding to the human melanocortin receptor subtypes. - Eur. J. Pharmacol., 1998, vol. 349(2-3), pp. 359-366.
• Schioth HB, Yook P, Muceniece R, Wikberg JE, Szardenings M. Chimeric melanocortin MC1 and MC3 receptors: identification of domains participating in binding of melanocyte-stimulating hormone peptide. - Mol. Pharmacol., 1998, vol. 54(1), pp.154-161.
• Prusis P, Schioth HB, Muceniece R, Herzyk P, Afshar M, Hubbard RE, Wikberg JE. Modelling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide. - J. Mol. Graph. Model., 1997, vol. 15(5), pp. 307-317.
• Schioth HB, Mutulis F, Muceniece R, Prusis P, Wikberg JE. Discovery of novel melanocortin4 receptor selective MSH analogues. - Br. J. Pharmacol., 1998, vol. 124(1), pp. 75-82.
• Schioth HB, Muceniece R, Wikberg JE. Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes. - Neuropeptides, 1997, vol. 31(6), pp.565-571.
• Schioth HB, Muceniece R, Larsson M, Wikberg JE. The melanocortin 1, 3, 4 or 5 receptors do not have a binding epitope for ACTH beyond the sequence of alpha-MSH.- J. Endocrinol., 1997, vol.155(1), pp.73-78.
• Schioth HB, Muceniece R, Mutulis F, Prusis P, Lindeberg G, Sharma SD, Hruby VJ, Wikberg JE.Selectivity of cyclic [D-Nal7] and [D-Phe7] substituted MSH analogues for the melanocortin receptor subtypes. - Peptides, 1997, vol.18(7), pp. 1009-1013.
• Szardenings M, Tornroth S, Mutulis F, Muceniece R, Keinanen K, Kuusinen A, Wikberg JE. Phage display selection on whole cells yields a peptide specific for melanocortin receptor 1. - J Biol. Chem., 1997, vol. 272(44), pp.27943-27948.
• Schioth HB, Petersson S, Muceniece R, Szardenings M, Wikberg JE. Deletions of the N-terminal regions of the human melanocortin receptors. - FEBS Lett., vol. 410(2-3), pp.223-8.
• Schioth HB, Muceniece R, Szardenings M, Prusis P, Lindeberg G, Sharma SD, Hruby VJ, Wikberg JE. Characterisation of D117A and H260A mutations in the melanocortin 1 receptor. - Mol .Cell Endocrinol., 1997, vol.126(2), pp.213-219.
• Schioth HB, Muceniece R, Larsson M, Mutulis F, Szardenings M, Prusis P, Lindeberg G, Wikberg JE. Binding of cyclic and linear MSH core peptides to the melanocortin receptor subtypes. - Eur. J. Pharmacol., 1997, vol. 319(2-3), pp. 369-373.
• Schioth HB, Muceniece R, Wikberg JE. Selectivity of [Phe-I7], [Ala6], and [D-Ala4,Gln5,Tyr6] substituted ACTH(4-10) analogues for the melanocortin receptors. - Peptides, 1997, vol.18(5), pp.761-763.
• Schioth HB, Muceniece R, Szardenings M, Prusis P, Wikberg JE. Evidence indicating that the TM4, EL2, and TM5 of the melanocortin 3 receptor do not participate in ligand binding. - Biochem. Biophys. Res. Commun., 1996, vol. 229(3), pp. 687-692.
• Schioth HB, Muceniece R, Wikberg JE, Szardenings M. Alternative translation initiation codon for the human melanocortin MC3 receptor does not affect the ligand binding.- Eur. J. Pharmacol., 1996, vol. 314(3), pp.381-384.
• Schioth HB, Muceniece R, Wikberg JE. Characterisation of the melanocortin 4 receptor by radioligand binding. - Pharmacol. Toxicol., 1996 , vol. 79(3), pp. 161-165.
• Schioth HB, Kuusinen A, Muceniece R, Szardenings M, Keinanen K, Wikberg JE. Expression of functional melanocortin 1 receptors in insect cells. - Biochem. Biophys. Res. Commun., 1996, vol. 221(3), pp. 807-814.
• Chhajlani V, Muceniece R, Wikberg JE. Molecular cloning of a novel human melanocortin receptor. - Biochem. Biophys. Res. Commun., 1996, vol. 218(2), p. 638.
• Xia Y, Muceniece R, Wikberg JE. Immunological localisation of melanocortin 1 receptor on the cell surface of WM266-4 human melanoma cells. - Cancer Lett.,1996, vol. 98(2), pp.157-162.
• Schioth HB, Chhajlani V, Muceniece R, Klusa V, Wikberg JES. Major pharmacological distinction of the ACTH receptor from other melanocortin receptors. - Life Sci., 1996, vol. 59(10), pp.797-801.
• Uhlen S, Muceniece R, Rangel N, Tiger G, Wikberg JE. Comparison of the binding activities of some drugs on alpha 2A, alpha 2B and alpha 2C-adrenoceptors and non-adrenergic imidazoline sites in the guinea pig. - Pharmacol. Toxicol., 1995, vol. 76(6), pp.353-364.
• Prusis P, Frandberg PA, Muceniece R, Kalvinsh I, Wikberg JE. A three dimensional model for the interaction of MSH with the melanocortin-1 receptor. - Biochem. Biophys. Res. Commun., 1995, vol. 210(1), pp. 205-210.
• Schioth HB, Muceniece R, Wikberg JE, Chhajlani . Characterisation of melanocortin receptor subtypes by radioligand binding analysis. - Eur. J. Pharmacol., 1995, vol. 288(3), pp. 311-317.
• Xia Y, Skoog V, Muceniece R, Chhajlani V, Wikberg JE. Polyclonal antibodies against human melanocortin MC1 receptor: preliminary immunohistochemical localisation of melanocortin MC1 receptor to malignant melanoma cells. - Eur. J. Pharmacol.,1995, vol. 288(3), pp. 277-283.
• Frandberg PA, Muceniece R, Prusis P, Wikberg J, Chhajlani V. Evidence for alternate points of attachment for alpha-MSH and its stereoisomer [Nle4, D-Phe7]-alpha-MSH at the melanocortin-1 receptor. - Biochem. Biophys. Res. Commun., 1994, vol. 202(3), pp. 1266-1271.
• Chhajlani V, Muceniece R, Wikberg JE. Molecular cloning of a novel human melanocortin receptor. - Biochem. Biophys. Res. Commun., 1993, vol.195(2), pp. 866-873.

Patents:

• WO01/36980: A process for identifying the active site in a biological target.
  T.Lundstedt, P.Andersson, J.Wikberg, R.Muceniece, P.Prusis.

• EP1025127A1: MSH-receptor subtype selective cyclic peptides.
  Wikberg, J., Muceniece, R., Mutulis, F., Prusis, P., Schiöth. H-B.
• WO035952A2: Compunds fpr control of eating, growth and body weight.
  Wikberg, J., Mutulis, F., Mutule, I., Schiöth, H., Muceniece, R.
• AU3722299A1: Melanocortin 1 receptor selective compounds.
  M. Szardenings, R. Muceniece, I. Mutule, F. Mutulis, J. Wikberg.
• WO9957148A1: Melanocortin 1 receptor selective compounds.
  M. Szardenings, R. Muceniece, I. Mutule, F. Mutulis, J. Wikberg.
• AU6127498A1: MSH-receptor subtype selective cyclic peptides.
  Wikberg, J., Muceniece, R., Mutulis, F., Prusis, P., Schiöth. H-B.
• WO9837097A1: MSH-receptor subtype selective cyclic peptides.
  Wikberg, J., Muceniece, R., Mutulis, F., Prusis, P., Schiöth. H-B.
• SE9700620AO: Cykliska peptider med selektivitet föer MSH-recepåtor subtyper.
  R. Muceniece, F. Mutulis, P. Prusis, H-B. Schiöth, J. Wikberg.

Research Projects:

• R.Muceniece (Head of Project). Role of Melanocortins and Their   Synthetic  Mimetics in Neuro-Immuno-Endocrine Network. Latvian Council of Science.(2005 -  `)
• R.Muceniece (Head of Project). Neuroinflammation and Immune Responses: Control by Melanocortins and Their Mimetics. Latvian Council of Science.(2001 - 2004 )
• R.Muceniece (Program Coordinator). Visby Network Grant: Program for Education and Development of Novel Technologies for Drug Development. 

Last update 19.12.2007