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[ 3 H]Dipyridamole Binding to Guinea Pig Brain Membranes: Possible Heterogeneity of Central Adenosine Uptake Sites
Author(s) -
Marangos Paul J.,
Deckert Jurgen
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05651.x
Subject(s) - adenosine , verapamil , chemistry , ligand (biochemistry) , binding site , nimodipine , guinea pig , dipyridamole , stereochemistry , nifedipine , membrane , biophysics , pharmacology , calcium , biochemistry , receptor , medicine , endocrinology , biology , organic chemistry
The binding of [ 3 H]dipyridamole ([ 3 H]DPR) to guinea pig brain membranes is described and compared to that of [ 3 H]nitrobenzylthioinosine ([ 3 H]NBI). The binding of [ 3 H]DPR is saturable, reversible, and specific with phar‐macologic evidence indicating that this ligand is binding to the adenosine uptake site. Compared to [ 3 H]NBI the binding of [ 3 H]DPR is of higher capacity (B max = 208 ±16 fmol/ mg protein for [ 3 H]NBI and 530 ± 40 fmol/mg protein for [ 3 H]DPR) and lower affinity ( K D = 0.35 ± 0.02 n M for [ 3 H]NBI and 7.6 ± 0.7 n M for [ 3 H]DPR). The adenosine uptake inhibitors are the most potent inhibitors of binding ( K i of 10 −8 ‐10 −7 M ) whereas adenosine receptor ligands such as cyclohexyladenosine, 2‐chloroadenosine, and various methylxanthines are several orders of magnitude less potent ( K i 10 −5 ‐10 −2 ). The inhibition of [ 3 H]DPR binding by NBI is biphasic, with only 40% of binding being susceptible to inhibition by NBI concentrations < 10 −5 M . The tissue distribution of [ 3 H]DPR binding parallels that of [ 3 H]NBI although in most cases significantly more sites are observed with [ 3 H]DPR. Calcium channel blocking agents such as nifedipine, nimodipine, and verapamil are also inhibitors of [ 3 H]DPR binding with potencies in the micromolar range. The data are consistent with [ 3 H]DPR being a useful additional ligand for the adenosine uptake site and provide evidence that multiple uptake binding sites exist of which only about 40% are NBI‐sensitive.