Summary Although the endocannabinoid anandamide is frequently described to act predominantly in the cardiovascular system, the molecular mechanisms of its signaling remained unclear. In human endothelial cells, two receptors for anandamide were found, which were characterized as cannabinoid 1 receptor (CB1R; CNR1) and G-protein-coupled receptor 55 (GPR55). Both receptors trigger distinct signaling pathways. It crucially depends on the activation status of integrins which signaling cascade becomes promoted upon anandamide stimulation. Under conditions of inactive integrins, anandamide initiates CB1R-derived signaling, including Gi-protein-mediated activation of spleen tyrosine kinase (Syk), resulting in NFκB translocation. Furthermore, Syk inhibits phosphoinositide 3-kinase (PI3K) that represents a key protein in the transduction of GPR55-originated signaling. However, once integrins are clustered, CB1R splits from integrins and, thus, Syk cannot further inhibit GPR55-triggered signaling resulting in intracellular Ca2+ mobilization from the endoplasmic reticulum (ER) via a PI3K-Bmx-phospholipase C (PLC) pathway and activation of nuclear factor of activated T-cells. Altogether, these data demonstrate that the physiological effects of anandamide on endothelial cells depend on the status of integrin clustering.

Synthesis, Structural Analysis and Pharmacological Effects of N2-Substituted 3,4-Dihydrobenzo(h)quinolin-2-amines.-The title compound (VIa) displays antiarrhythmic effect at the papillary muscle of guinea pigs and reduces moderately the heart rate in rats. -(WENDELIN, W.; KEIMELMAYR, H.; GOESSNITZER, E.; ABOU EL ELLA, D.; Pharmazie 51 (1996) 11, 816-822; Inst. Pharm. Chem., Karl-Franzens-Univ., A-8010 Graz, Austria; EN)

Fused pyrimidine derivativesFused pyrimidine derivatives R 0515 Novel High Energy Intermediate Analogues with Triazasterol-Related Structures as Potential Inhibitors of the Ergosterol Biosynthesis. Part 2. Optimization of the Synthesis of 1,6,7,11b-Tetrahydro-2H-pyrimido[4,3-a] Isoquinolin-4-amines as Parent Compounds of Novel 8,13,15-Triazasteroids. -The desired products such as (XI) and (XII) and the intermediates (VI) only show weak inhibitory activity in an antifungal assay. -(GOESSNITZER*, E.; PUNKENHOFER, A.; Monatsh. Chem. 134 (2003) 6, 909-927; Inst. Pharm. Chem., Karl-Franzens-Univ., A-8010 Graz, Austria; Eng.) -K. Schneider 38-138

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Bridged Derivatives of Phenyl-and Naphthylethylamine and Nitrogen Analogous Compounds. Part 5. Synthesis, Structure and Pharmacological Effects of N3-Substituted 1,2-Dihydrobenzo(f )quinolin-3amines.-The synthesis of the amine-derived hydroiodides (VII) is described. Liberation of the free amine (VIII) is accompanied by tautomerism. -(WENDELIN, W.; ZARFL, J.; GOESSNITZER, E.; EL ELLA, D. A.; Sci.