Pharmacological characterization of the adenylate cyclase-coupled
adenosine receptor in isolated guinea pig atrial myocytes
A. Wilken, H. Tawfik-Schlieper, K. Klotz, and U. Schwabe. Mol Pharmacol, 37 (6):
916-20(June 1990)Wilken, A Tawfik-Schlieper, H Klotz, K N Schwabe, U Research Support,
Non-U.S. Gov't United states Molecular pharmacology Mol Pharmacol.
1990 Jun;37(6):916-20..
Abstract
Although adenosine is known to activate K+ conduction in atrial tissue,
there is still debate as to the involvement of cAMP-dependent mechanisms.
In isolated adult guinea pig atrial myocytes, we demonstrate that
the highly A1-selective adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine
reduced basal cAMP levels by 30-40% in the absence and presence of
the nonxanthine phosphodiesterase inhibitor Ro 20-1724. Isoprenaline
caused a concentration-dependent increase in cAMP levels, which was
more pronounced in the presence of the phosphodiesterase inhibitor.
Several adenosine derivatives suppressed the isoprenaline-induced
cAMP increase by approximately 80%. The rank order of potency was
2-chloro-N6-cyclopentyladenosine (IC50, 93 nM) greater than (R)-N6-phenylisopropyladenosine
(IC50, 309 nM) greater than 5'-N-ethylcarboxamidoadenosine (IC50,
813 nM) much greater than (S)-N6-phenylisopropyladenosine (IC50,
26,300 nM). A similar but complete suppression of the isoprenaline-induced
cAMP increase was produced by the muscarinic receptor agonist carbachol
(IC50, 398 nM), which like adenosine is known to activate atrial
K+ channels. The A1-adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine
antagonized the effect of 2-chloro-N6-cyclopentyladenosine concentration-dependently,
with a KB value of 9.6 nM. In atrial myocytes isolated from guinea
pigs pretreated with pertussis toxin, the inhibitory effects of adenosine
analogs on basal and isoprenaline-stimulated cAMP accumulation were
markedly attenuated. It is concluded that the adenosine receptor
in guinea pig atrial myocytes, which is known to be linked to K+
channels, is also coupled to adenylate cyclase via a pertussis toxin-sensitive
guanine nucleotide-binding protein and shows the characteristics
of the A1-adenosine receptor subtype.
Wilken, A Tawfik-Schlieper, H Klotz, K N Schwabe, U Research Support,
Non-U.S. Gov't United states Molecular pharmacology Mol Pharmacol.
1990 Jun;37(6):916-20.
%0 Journal Article
%1 Wilken1990
%A Wilken, A.
%A Tawfik-Schlieper, H.
%A Klotz, K. N.
%A Schwabe, U.
%D 1990
%J Mol Pharmacol
%K & *Cyclic 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology AMP AMP/metabolism Adenosine/analogs Adenylate Animals Atria/*metabolism Bordetella/pharmacology Carrier Cyclase Cyclase/*metabolism Cyclic Factors, Female Guinea Heart Isoproterenol/pharmacology Male Myocardium/cytology/*metabolism Pertussis Pigs Protein Proteins/drug Receptor Toxin Virulence derivatives/pharmacology effects/*metabolism
%N 6
%P 916-20
%T Pharmacological characterization of the adenylate cyclase-coupled
adenosine receptor in isolated guinea pig atrial myocytes
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2163017
%V 37
%X Although adenosine is known to activate K+ conduction in atrial tissue,
there is still debate as to the involvement of cAMP-dependent mechanisms.
In isolated adult guinea pig atrial myocytes, we demonstrate that
the highly A1-selective adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine
reduced basal cAMP levels by 30-40% in the absence and presence of
the nonxanthine phosphodiesterase inhibitor Ro 20-1724. Isoprenaline
caused a concentration-dependent increase in cAMP levels, which was
more pronounced in the presence of the phosphodiesterase inhibitor.
Several adenosine derivatives suppressed the isoprenaline-induced
cAMP increase by approximately 80%. The rank order of potency was
2-chloro-N6-cyclopentyladenosine (IC50, 93 nM) greater than (R)-N6-phenylisopropyladenosine
(IC50, 309 nM) greater than 5'-N-ethylcarboxamidoadenosine (IC50,
813 nM) much greater than (S)-N6-phenylisopropyladenosine (IC50,
26,300 nM). A similar but complete suppression of the isoprenaline-induced
cAMP increase was produced by the muscarinic receptor agonist carbachol
(IC50, 398 nM), which like adenosine is known to activate atrial
K+ channels. The A1-adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine
antagonized the effect of 2-chloro-N6-cyclopentyladenosine concentration-dependently,
with a KB value of 9.6 nM. In atrial myocytes isolated from guinea
pigs pretreated with pertussis toxin, the inhibitory effects of adenosine
analogs on basal and isoprenaline-stimulated cAMP accumulation were
markedly attenuated. It is concluded that the adenosine receptor
in guinea pig atrial myocytes, which is known to be linked to K+
channels, is also coupled to adenylate cyclase via a pertussis toxin-sensitive
guanine nucleotide-binding protein and shows the characteristics
of the A1-adenosine receptor subtype.
@article{Wilken1990,
abstract = {Although adenosine is known to activate K+ conduction in atrial tissue,
there is still debate as to the involvement of cAMP-dependent mechanisms.
In isolated adult guinea pig atrial myocytes, we demonstrate that
the highly A1-selective adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine
reduced basal cAMP levels by 30-40% in the absence and presence of
the nonxanthine phosphodiesterase inhibitor Ro 20-1724. Isoprenaline
caused a concentration-dependent increase in cAMP levels, which was
more pronounced in the presence of the phosphodiesterase inhibitor.
Several adenosine derivatives suppressed the isoprenaline-induced
cAMP increase by approximately 80%. The rank order of potency was
2-chloro-N6-cyclopentyladenosine (IC50, 93 nM) greater than (R)-N6-phenylisopropyladenosine
(IC50, 309 nM) greater than 5'-N-ethylcarboxamidoadenosine (IC50,
813 nM) much greater than (S)-N6-phenylisopropyladenosine (IC50,
26,300 nM). A similar but complete suppression of the isoprenaline-induced
cAMP increase was produced by the muscarinic receptor agonist carbachol
(IC50, 398 nM), which like adenosine is known to activate atrial
K+ channels. The A1-adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine
antagonized the effect of 2-chloro-N6-cyclopentyladenosine concentration-dependently,
with a KB value of 9.6 nM. In atrial myocytes isolated from guinea
pigs pretreated with pertussis toxin, the inhibitory effects of adenosine
analogs on basal and isoprenaline-stimulated cAMP accumulation were
markedly attenuated. It is concluded that the adenosine receptor
in guinea pig atrial myocytes, which is known to be linked to K+
channels, is also coupled to adenylate cyclase via a pertussis toxin-sensitive
guanine nucleotide-binding protein and shows the characteristics
of the A1-adenosine receptor subtype.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Wilken, A. and Tawfik-Schlieper, H. and Klotz, K. N. and Schwabe, U.},
biburl = {https://www.bibsonomy.org/bibtex/22d02a54ad116372aca603e85bdb4f17b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {d473930b79774152c87a98ddb2da8ff1},
intrahash = {2d02a54ad116372aca603e85bdb4f17b},
issn = {0026-895X (Print) 0026-895X (Linking)},
journal = {Mol Pharmacol},
keywords = {& *Cyclic 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology AMP AMP/metabolism Adenosine/analogs Adenylate Animals Atria/*metabolism Bordetella/pharmacology Carrier Cyclase Cyclase/*metabolism Cyclic Factors, Female Guinea Heart Isoproterenol/pharmacology Male Myocardium/cytology/*metabolism Pertussis Pigs Protein Proteins/drug Receptor Toxin Virulence derivatives/pharmacology effects/*metabolism},
month = Jun,
note = {Wilken, A Tawfik-Schlieper, H Klotz, K N Schwabe, U Research Support,
Non-U.S. Gov't United states Molecular pharmacology Mol Pharmacol.
1990 Jun;37(6):916-20.},
number = 6,
pages = {916-20},
shorttitle = {Pharmacological characterization of the adenylate cyclase-coupled
adenosine receptor in isolated guinea pig atrial myocytes},
timestamp = {2010-12-14T18:19:00.000+0100},
title = {Pharmacological characterization of the adenylate cyclase-coupled
adenosine receptor in isolated guinea pig atrial myocytes},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2163017},
volume = 37,
year = 1990
}