Mechanism of A2 adenosine receptor activation. I. Blockade of A2
adenosine receptors by photoaffinity labeling
M. Lohse, K. Klotz, and U. Schwabe. Mol Pharmacol, 39 (4):
517-23(April 1991)Lohse, M J Klotz, K N Schwabe, U United states Molecular pharmacology
Mol Pharmacol. 1991 Apr;39(4):517-23..
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).
%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
}