Matthias Kotthoff

Publications (3) View all

• Article: Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2.

  Agne Babusyte, Matthias Kotthoff, Julia Fiedler, Dietmar Krautwurst
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  ABSTRACT: Certain biogenic amines, such as 2-PEA, TYR, or T1AM, modulate blood pressure, cardiac function, brain monoaminergic systems, and olfaction-guided behavior by specifically interacting with members of a group of rhodopsin-like receptors, TAAR. A receptor that is absent from olfactory epithelia but had long been identified in the brain and a variety of peripheral tissues, TAAR1 has been found recently in blood B cells, suggesting a functional role of TAAR1 in these cells. With the present study, we have set out to clarify the expression and functional roles of TAAR in different isolated human blood leukocyte types. Here, we report the functional expression of TAAR1 and its closest relative TAAR2 in blood PMN and T and B cells. Both receptors are coexpressed in a subpopulation of PMN, where they are necessary for the chemosensory migration toward the TAAR1 ligands 2-PEA, TYR, and T1AM, with EC(50) values of 0.43 ± 0.05 nM, 0.52 ± 0.05 nM, and 0.25 ± 0.04 nM, respectively. The same amines, with similar potencies, triggered cytokine or Ig secretion, in purified blood T or B cells, respectively. Notably, 2-PEA regulated mRNA expression of 28 T cell function-related genes, above all of the CCL5. In siRNA-guided experiments, TAAR1 and TAAR2 proved to be necessary for amine-induced blood leukocyte functions. In summary, our results demonstrate that biogenic amines potently regulate blood cell functions via TAAR1 and TAAR2 and open the perspective of their specific pharmacological modulation.
  Journal of leukocyte biology 01/2013; · 4.99 Impact Factor
• Article: A hit map-based statistical method to predict best ligands for orphan olfactory receptors: natural key odorants versus "lock picks".

  Dietmar Krautwurst, Matthias Kotthoff
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  ABSTRACT: Smell is a multidimensional chemical sense. It creates a perception of our odorous environment by integrating the information of a plethora of volatile chemicals with other sensory inputs, emotions and memories. We are almost always exposed to odorant mixtures, not just single chemicals. Olfactory processing of complex odorant mixtures, such as coffee or wine, first is decoded at the site of perception by the hundreds of different olfactory receptor types, each residing in the cilia of their olfactory sensory neurons in the nose. Often, only a few odorants from many are essential to determine complex olfactory perception. But merely using the chemical structure of odorants is insufficient to identify and predict characteristic odor qualities and low odor thresholds. An understanding of odorant coding critically depends on knowledge about the interaction of key odorants of biologically relevant odor bouquets with their best cognate receptors. Here, we describe a hit map-based method of correlating the information content of all bioassay-tested odorants with their cognate odorant-receptor frequency in four phylogenetic subsets of human olfactory/chemosensory receptors.
  Methods in molecular biology (Clifton, N.J.) 01/2013; 1003:85-97.
• Conference Proceeding: Human Olfactory Receptors for Thiol Key Food Odorants

  Matthias Kotthoff, Peter Schieberle, Dietmar Krautwurst
  9th Wartburg Symposium on Flavor Chemistry and Biology9th Wartburg Symposium on Flavor Chemistry and Biology, Eisenach, Germany; 01/2011