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Barbiturates Are Selective Antagonists at A 1 Adenosine Receptors
Author(s) -
Lohse M. J.,
Klotz K.N.,
Jakobs K. H.,
Schwabe U.
Publication year - 1985
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.1471-4159.1985.tb10532.x
Subject(s) - chemistry , adenosine , receptor , adenosine receptor , pharmacology , adenosine a2b receptor , adenylate kinase , cyclase , stimulation , antagonism , pentobarbital , stereochemistry , biochemistry , biology , endocrinology , agonist
Barbiturates in pharmacologically relevant concentrations inhibit binding of ( R )‐ N 6 ‐phenylisopropyl[ 3 H]adenosine ([ 3 H]PIA) to solubilized A 1 adenosine receptors in a concentration‐dependent, stereospecific, and competitive manner. K i values are similar to those obtained for membrane‐bound receptors and are 31 μ M for (±)‐5‐(1,3‐dimethyl)‐5‐ethylbarbituric acid [(±)‐DMBB] and 89 μ M for (±)‐pentobarbital. Kinetic experiments demonstrate that barbiturates compete directly for the binding site of the receptor. The inhibition of rat striatal adenylate cyclase by unlabelled ( R )‐ N 6 ‐phenyl‐isopropyladenosine [( R )‐PIA] is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A 2 adenosine receptors in membranes from N1E 115 neuroblastoma cells is antagonized only by 10–30 times higher concentrations of barbiturates. It is concluded that barbiturates are selective antagonists at the A 1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A 1 adenosine receptor antagonism may convey excitatory properties to barbiturates.