TY  - JOUR
A1  - Lohse, M. J.
A1  - Klotz, Karl-Norbert
A1  - Lindenborn Fotinos, J.
A1  - Reddington, M.
A1  - Schwabe, U.
A1  - Olsson, R. A.
T1  - 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) - a selective high affinity antagonist radioligand for A\(_1\) adenosine receptors
N2  - The properties of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as an antagonist ligand for A\(_1\) adenosirre receptors were examined and conipared with other radioligands for this receptor. DPCPX competitively antagonized both the inhibition of adenylate cyclase activity via A\(_1\) adenosirre receptors and the stimulationvia A\(_2\) adenosirre receptors. The K\(_i\)-values of this antagonism were 0.45 nM at the A\(_1\) receptor of rat fat cells, and 330 nM at the A\(_2\) receptor of human platelets, giving a more than 700-fold A\(_1\)-selectivity. A similar A\(_1\)-selectivity was determined in radioligand binding studies. Even at high concentrations, DPCPX did not significantly inhibit the soluble cAMPphosphodiesterase activity of human platelets. [\(^3\)H]DPCPX (105 Ci/mmol) bound in a saturable manner with high affinity to A\(_1\) receptors in membranes of bovine brain and heart, and rat brain and fat cells (K\(_D\) -values 50-190 pM). Its nonspecific binding was about 1% of total at K\(_D\) , except in bovine myocardial membranes (about 10%). Binding studies with bovine myocardial membranes allowed the analysis of both the high and low agonist affinity states of this receptor in a tissue with low receptor density. The binding properties of [\(^3\)H]DPCPX appear superior to those of other agonist and antagonist radioligands for the A\(_1\) receptor.
KW  - Toxikologie
KW  - Adenosine receptors
KW  - Adenylate cyclase
KW  - Phosphodiesterase
KW  - Xanthines
KW  - Radioligands
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60246
ER  - 
TY  - JOUR
A1  - Reddington, M.
A1  - Klotz, Karl-Norbert
A1  - Lohse, M. J.
A1  - Hietel, B.
T1  - Radiation inactivation analysis of the A\(_1\) adenosine receptor: decrease in radiation inactivation size in the presence of guanine nucleotide
N2  - Radiation inactivation analysis of the binding of the A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes yielded a radiation inactivation size of 58 kDa. In the presence of GTPyS this was reduced to 33 kDa, in good agreement with the size of the ligand-binding subunit detected after photoaffinity labelling. The data indicate that the structural association of A\(_1\) adenosine receptors with G-protein components is altered in situ in the presence of guanine nucleotides.
KW  - Toxikologie
KW  - Adenosine receptor
KW  - A1
KW  - Radiation inactivation
KW  - Target size
KW  - G-protein
KW  - (Rat brain membrane)
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60318
ER  -