Lasius neglectus (Hymenoptera: Formicidae) – a widely distributed tramp species in Central Asia.

Abstract Departing from the assumed origin in Asia Minor or the Middle East, Lasius neglectu

Title Page Probing ligand-specific histamine H 1 -and H 2 -receptor conformations with N G -acylated imidazolylpropylguanidines Running Title Page Running title: Ligand-specific histamine receptor conformations

G sαS , fusion protein of the guinea pig histamine H 2 -receptor and the short splice variant of G sα ; GTPγS, guanosine 5'-[γ-thio]triphosphate; hH 1 R, human histamine H 1 -receptor; hH 2 R, human histamine H 2 -receptor; hH 2 R-G sαS , fusion protein of the human histamine H 2 -receptor and the short splice variant of G sα ; HIS, histamine; IMP, impromidine; RGS protein, regulator of G-protein signaling; rH 2 R, rat histamine H 2 -receptor; TM, transmembrane domain. Section: Cellular & Molecular JPET #97923 3 Abstract Impromidine (IMP) and arpromidine (ARP)-derived guanidines are more potent and efficacious guinea pig (gp) histamine H 2 -receptor (gpH 2 R)-than human (h) H 2 R agonists and histamine H 1 -receptor (H 1 R) antagonists with preference for hH 1 R relative to gpH 1 R. We examined N G -acylated imidazolylpropylguanidines (AIPGs) which are less basic than guanidines at hH 2 R, gpH 2 R, rat H 2 R (rH 2 R), hH 1 R and gpH 1 R expressed in Sf9 cells as probes for ligand-specific receptor conformations. AIPGs were similarly potent H 2 R agonists as the corresponding guanidines IMP and ARP, respectively. Exchange of pyridyl in ARP against phenyl increased AIPG potency ten-fold, yielding the most potent agonists at the hH 2 R-G sα fusion protein and gpH 2 R-G sα identified so far. Some AIPGs were similarly potent and efficacious at hH 2 R-G sα and gpH 2 R-G sα . AIPGs stabilized the ternary complex in hH 2 R-G sα and gpH 2 R-G sα differently than the corresponding guanidines. Guanidines, AIPGs and small H 2 R agonists exhibited distinct agonist properties at hH 2 R, gpH 2 R and rH 2 R measuring adenylyl cyclase activity. In contrast to ARP and IMP, AIPGs were partial H 1 R agonists exhibiting higher efficacies at hH 1 R than at gpH 1 R. This is remarkable since so far, all bulky H 1 R agonists exhibited higher efficacies at gpH 1 R than at hH 1 R. Collectively, our data suggest that AIPGs stabilize different active conformations in hH 2 R, gpH 2 R and rH 2 R than guanidines and that in contrast to guanidines, AIPGs are capable of stabilizing a partially active state of hH 1 R. JPET #97923

Molecular analysis of the interaction of anthrax adenylyl cyclase toxin, edema factor, with 2(3)-O-(N-methyl)anthraniloyl)-substituted purine and pyrimidine nucleotides.

Abbreviations AC, adenylyl cyclase; ANT, anthraniloyl-; CaM, calmodulin; CyaA, Bordetella pertussis adenylyl cyclase toxin; ESI, electrospray ionization; FRET, fluorescence resonance energy transfer; HPLC, high pressure liquid chromatography; k, capacity factor; mAC, mammalian membranous adenylyl cyclase; MANT, methylanthraniloyl-; MS, mass spectroscopy; MW, molecular weight; NDP, nucleoside 5´-diphosphate; NTP, nucleoside 5´-triphosphate; PMEApp, {9-[2-(phosphonomethoxy)ethyl]adenine diphosphate}; EF, full-length edema factor adenylyl cyclase toxin; EF3, catalytic domain of edema factor adenylyl cyclase toxin; R f , retention factor; R t , retention time; TLC, thin layer chromatography. MOL #52340 3 Abstract Bacillus anthracis causes anthrax disease and exerts its deleterious effects by the release of three exotoxins, i.e. lethal factor, protective antigen and edema factor EF), a highly active calmodulin-dependent adenylyl cyclase (AC). However, conventional antibiotic treatment is ineffective against either toxemia or antibioticresistant strains. Thus, more effective drugs for anthrax treatment are needed. Previous studies from our laboratory showed that mammalian membranous A

Zur Geschichte des Grasser Berges : Zugleich ein Beitrag zur Schottenmission und Konradinergut

Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a) receptor. CT(a)R downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours) and prolonged (up to 72 hours) stimulation. CT(a)R kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(a)R downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo