%0 Journal Article %1 Lohse1985 %A Lohse, M. J. %A Klotz, K. N. %A Jakobs, K. H. %A Schwabe, U. %D 1985 %J J Neurochem %K & Adenylate Animals Barbiturates/*pharmacology Cell Corpus Cyclase/metabolism GABA-A/metabolism Humans Line Male Neuroblastoma/enzymology/metabolism Phenobarbital/analogs Phenylisopropyladenosine/metabolism Purinergic Rats Relationship Strains Striatum/enzymology/metabolism Structure-Activity Surface/*antagonists derivatives/pharmacology inhibitors/metabolism Receptor Mice %N 6 %P 1761-70 %T Barbiturates are selective antagonists at A1 adenosine receptors %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2997396 %V 45 %X Barbiturates in pharmacologically relevant concentrations inhibit binding of (R)-N6-phenylisopropyl3Hadenosine (3HPIA) to solubilized A1 adenosine receptors in a concentration-dependent, stereospecific, and competitive manner. Ki values are similar to those obtained for membrane-bound receptors and are 31 microM for (+/-)-5-(1,3-dimethyl)-5-ethylbarbituric acid (+/-)-DMBB and 89 microM 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)-N6-phenylisopropyladenosine (R)-PIA is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A2 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 A1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A1 adenosine receptor antagonism may convey excitatory properties to barbiturates.

@article{Lohse1985, abstract = {Barbiturates in pharmacologically relevant concentrations inhibit binding of (R)-N6-phenylisopropyl[3H]adenosine ([3H]PIA) to solubilized A1 adenosine receptors in a concentration-dependent, stereospecific, and competitive manner. Ki values are similar to those obtained for membrane-bound receptors and are 31 microM for (+/-)-5-(1,3-dimethyl)-5-ethylbarbituric acid [(+/-)-DMBB] and 89 microM 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)-N6-phenylisopropyladenosine [(R)-PIA] is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A2 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 A1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A1 adenosine receptor antagonism may convey excitatory properties to barbiturates.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Klotz, K. N. and Jakobs, K. H. and Schwabe, U.}, biburl = {https://www.bibsonomy.org/bibtex/226f8f3e36fed47ce3afbdac507cfe5d0/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {dfca2dd4aa147009d1a4121f72ef2682}, intrahash = {26f8f3e36fed47ce3afbdac507cfe5d0}, issn = {0022-3042 (Print) 0022-3042 (Linking)}, journal = {J Neurochem}, keywords = {& Adenylate Animals Barbiturates/*pharmacology Cell Corpus Cyclase/metabolism GABA-A/metabolism Humans Line Male Neuroblastoma/enzymology/metabolism Phenobarbital/analogs Phenylisopropyladenosine/metabolism Purinergic Rats Relationship Strains Striatum/enzymology/metabolism Structure-Activity Surface/*antagonists derivatives/pharmacology inhibitors/metabolism Receptor Mice}, month = Dec, note = {Lohse, M J Klotz, K N Jakobs, K H Schwabe, U Research Support, Non-U.S. Gov't United states Journal of neurochemistry J Neurochem. 1985 Dec;45(6):1761-70.}, number = 6, pages = {1761-70}, shorttitle = {Barbiturates are selective antagonists at A1 adenosine receptors}, timestamp = {2010-12-14T18:22:56.000+0100}, title = {Barbiturates are selective antagonists at A1 adenosine receptors}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2997396}, volume = 45, year = 1985 }