%0 Journal Article %1 Lohse1991 %A Lohse, M. J. %A Klotz, K. N. %A Schwabe, U. %D 1991 %J Mol Pharmacol %K & Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Agents/metabolism Alprostadil/pharmacology Assay Azides/metabolism/*pharmacology Blood Cyclase/metabolism/physiology Humans Kinetics Membranes/metabolism Phenylisopropyladenosine/*analogs Platelets/metabolism/ultrastructure Purinergic/*antagonists Radioligand Tritium/diagnostic Vasodilator Xanthines/metabolism derivatives/metabolism/pharmacology inhibitors/physiology use Receptor %N 4 %P 517-23 %T Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2017151 %V 39 %X It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine (R)-AHPIA into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels Mol. Pharmacol. 30:403-409 (1986). In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling, which is described in the accompanying paper Mol. Pharmacol. 39:524-530 (1991).

@article{Lohse1991, abstract = {It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine [(R)-AHPIA] into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels [Mol. Pharmacol. 30:403-409 (1986)]. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling, which is described in the accompanying paper [Mol. Pharmacol. 39:524-530 (1991)].}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Lohse, M. J. and Klotz, K. N. and Schwabe, U.}, biburl = {https://www.bibsonomy.org/bibtex/284fbdbf99bd8e241d1c002eae51ab379/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {169acefd1eba5fd639e6df1dc1e2001e}, intrahash = {84fbdbf99bd8e241d1c002eae51ab379}, issn = {0026-895X (Print) 0026-895X (Linking)}, journal = {Mol Pharmacol}, keywords = {& Adenosine-5'-(N-ethylcarboxamide) Adenosine/analogs Adenylate Agents/metabolism Alprostadil/pharmacology Assay Azides/metabolism/*pharmacology Blood Cyclase/metabolism/physiology Humans Kinetics Membranes/metabolism Phenylisopropyladenosine/*analogs Platelets/metabolism/ultrastructure Purinergic/*antagonists Radioligand Tritium/diagnostic Vasodilator Xanthines/metabolism derivatives/metabolism/pharmacology inhibitors/physiology use Receptor}, month = Apr, note = {Lohse, M J Klotz, K N Schwabe, U United states Molecular pharmacology Mol Pharmacol. 1991 Apr;39(4):517-23.}, number = 4, pages = {517-23}, shorttitle = {Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling}, timestamp = {2010-12-14T18:20:06.000+0100}, title = {Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2017151}, volume = 39, year = 1991 }