Refine
Has Fulltext
- yes (52)
Is part of the Bibliography
- yes (52)
Year of publication
Document Type
Language
- English (52)
Keywords
- Toxikologie (32)
- Adenosine receptors (8)
- Adenosinrezeptor (5)
- Adenylate cyclase (4)
- G proteins (4)
- Pharmakologie (4)
- signal transduction (3)
- A1 adenosine receptors (2)
- Adenosin (2)
- G-protein (2)
- N-formyl peptides (2)
- Pharmazie (2)
- Radioligand binding (2)
- adenosine receptors (2)
- mast cells (2)
- membrane skeleton (2)
- (Rat brain membrane) (1)
- A(2B) receptors (1)
- A1 (1)
- A1 Adenosine receptors (1)
- A<sub>2</sub> Adenosine receptor (1)
- A\(_{2A}\) adenosine receptor antagonist (1)
- Adenosine receptor (1)
- Adenosine receptor antagonists (1)
- Atria (1)
- Barbiturat (1)
- Barbiturates (1)
- Chemotactic receptors (1)
- Cyclic AMP (1)
- Dermatologie (1)
- GABA-receptor complex (1)
- Human platelets (1)
- Immunologie (1)
- Ischemia/reperfusion (1)
- K + -channels (1)
- LTB4 receptor (1)
- Leukocyte/endothelium interaction (1)
- Lung (1)
- Mastzelle (1)
- Microcirculation (1)
- Molekularpharmakologie (1)
- N1E 115 cells (1)
- Niere (1)
- Phosphodiesterase (1)
- Photoaffinity labelling (1)
- Radiation inactivation (1)
- Radioligand binding - 86Rb + -efflux (1)
- Radioligands (1)
- Radioligauds (1)
- Ratte (1)
- Species differences (1)
- Target size (1)
- Theophylline (1)
- Venerologie (1)
- Xanthines (1)
- [3H]PIA binding (1)
- actin (1)
- adenosine (1)
- adenosine 3',5'-cyclic monophosphate (1)
- adenylate cyclase (1)
- agonists (1)
- antagonists (1)
- anti-Parkinson agents (1)
- anti-inflammatory agents (1)
- atopic eczema (1)
- barbiturates (1)
- binding affinity (1)
- brain membranes (1)
- calcium (1)
- chalcone (1)
- chemotactic receptors (1)
- chemotaxis (1)
- classification (1)
- coated vesicles (1)
- coumarin (1)
- cytoskeleton (1)
- desensitization (1)
- docking (1)
- drug (1)
- formyl peptides (1)
- gastrointestinal cancer (1)
- hA<sub>3</sub>AR (1)
- histamine release (1)
- human A(3) (1)
- human lung (1)
- indolylpyrimidylpiperazines (1)
- international union (1)
- molecular modeling (1)
- neurodegenerative diseases (1)
- neutrophils (1)
- partial agonists (1)
- phosphoinositides (1)
- photoaffinity labelling (1)
- potent (1)
- protein-coupled receptors (1)
- psoriasis (1)
- purine derivatives (1)
- radioligand (1)
- rat brain membranes (1)
- receptor binding (1)
- receptor solubilization (1)
- receptor-G protein coupling (1)
- receptor-G protein coupling. (1)
- receptors (1)
- solubilization (1)
- subtypes (1)
- targets (1)
- triazolotriazine derivatives (1)
Institute
In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A\(_2\) receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cycla.se, and platelet aggregation studies. Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited by compounds 2a-d with K\(_i\) values ranging from 2.8 to 16.4 nM. 2-Alkynyladenosines also exhibited high-affmity binding at solubilized A\(_2\) receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [\(^3\)H]DPCPX and for the agonist [\(^3\)H]CCPA gave K\(_i\) values in the nanomolar range, and the compounds showed moderate A\(_2\) selectivity. In order to improve this selectivity, the correaponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. A\(_1\) expected, the 5'-N-ethyluronamide derivatives retained the A\(_2\) affinity whereas the A\(_1\) affinity was attenuated, resulting in an up to 10-fold increase in A\(_2\) selectivity. A similar patternwas observed in adenylate cyclase assays andin platelet aggregation studies. A 30- to 45-fold selectivity for platelet A\(_2\) receptors compared to A\(_1\) receptors was found for compounds 8a-c in adenylate cyclase studies.
Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms.